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Journal articles on the topic 'Nicotine'
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1
Zenkner, Fernanda Fleig, Márcia Margis-Pinheiro, and Alexandro Cagliari. "Nicotine Biosynthesis in Nicotiana: A Metabolic Overview." Tobacco Science 56, no. 1 (April 1, 2019): 1–9. http://dx.doi.org/10.3381/18-063.
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Alkaloids are important compounds found in Nicotiana plants, essential in plant defense against herbivores. The main alkaloid of Nicotiana tabacum, nicotine, is produced in roots and translocated to the leaves. Nicotine is formed by a pyrrolidine and a pyridine ring in a process involving several enzymes. The pyridine ring of nicotine is derived from nicotinic acid, whereas the pyrrolidine ring originates from polyamine putrescine metabolism. After synthesis in root cortical cells, a set of transporters is known to transport nicotine upward to the aerial part and store it in leaf vacuoles. Moreover, nicotine can be metabolized in leaves, giving rise to nornicotine through the N-demethylation process. Some Nicotiana wild species produce acyltransferase enzymes, which allow the plant to make N-acyl-nornicotine, an alkaloid with more potent insecticidal properties than nicotine. However, although we can find a wealth of information about the alkaloid production in Nicotiana spp., our understanding about nicotine biosynthesis, transport, and metabolism is still incomplete. This review will summarize these pathways on the basis on recent literature, as well as highlighting questions that need further investigation.
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Page, Stephen J., Mingyan Zhu, and Suzanne M. Appleyard. "Effects of acute and chronic nicotine on catecholamine neurons of the nucleus of the solitary tract." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 316, no. 1 (January 1, 2019): R38—R49. http://dx.doi.org/10.1152/ajpregu.00344.2017.
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Nicotine is an addictive drug that has broad effects throughout the brain. One site of action is the nucleus of the solitary tract (NTS), where nicotine initiates a stress response and modulates cardiovascular and gastric function through nicotinic acetylcholine receptors (nAChRs). Catecholamine (CA) neurons in the NTS influence stress and gastric and cardiovascular reflexes, making them potential mediators of nicotine’s effects; however nicotine’s effect on these neurons is unknown. Here, we determined nicotine’s actions on NTS-CA neurons by use of patch-clamp techniques in brain slices from transgenic mice expressing enhanced green fluorescent protein driven by the tyrosine hydroxylase promoter (TH-EGFP). Picospritzing nicotine both induced a direct inward current and increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in NTS-CA neurons, effects blocked by nonselective nAChR antagonists TMPH and MLA. The increase in sEPSC frequency was mimicked by nAChRα7 agonist AR-R17779 and blocked by nAChRα7 antagonist MG624. AR-R17779 also increased the firing of TH-EGFP neurons, an effect dependent on glutamate inputs, as it was blocked by the glutamate antagonist NBQX. In contrast, the nicotine-induced current was mimicked by nAChRα4β2 agonist RJR2403 and blocked by nAChRα4β2 antagonist DHβE. RJR2403 also increased the firing rate of TH-EGFP neurons independently of glutamate. Finally, both somatodendritic and sEPSC nicotine responses from NTS-CA neurons were larger in nicotine-dependent mice that had under gone spontaneous nicotine withdrawal. These results demonstrate that 1) nicotine activates NTS-CA neurons both directly, by inducing a direct current, and indirectly, by increasing glutamate inputs, and 2) NTS-CA nicotine responsiveness is altered during nicotine withdrawal.
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Liu, Zhi, Yo Otsu, Cristina Vasuta, Hiroyuki Nawa, and Timothy H. Murphy. "Action-Potential-Independent GABAergic Tone Mediated by Nicotinic Stimulation of Immature Striatal Miniature Synaptic Transmission." Journal of Neurophysiology 98, no. 2 (August 2007): 581–93. http://dx.doi.org/10.1152/jn.00768.2006.
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Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where they can promote cell firing in hippocampal CA3 neurons. We have evaluated whether nicotine regulation of miniature synaptic activity can be extended to inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in acute brain slices. Bath application of micromolar nicotine typically induced 12-fold increases in the frequency of miniature inhibitory synaptic currents (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under these conditions. Nicotine stimulation of mIPSCs was dependent on entry of extracellular calcium because removal of calcium from perfusate was able to block its action. To assess the potential physiological significance of the nicotine-stimulated increase in mIPSC frequency, we also examined the nicotine effect on evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect could be attributed to two potential mechanisms: transmitter depletion due to extremely high mIPSC rates and/or a reduction in presynaptic excitability associated with nicotinic depolarization. Treatment with low concentrations of K+ was able to in part mimic nicotine's stimulatory effect on mIPSCs and inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct depolarizing action of nicotine that could dampen eIPSC activity leading to a switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.
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DeVito, Elise E., Kevin P. Jensen, Stephanie S. O’Malley, Ralitza Gueorguieva, Suchitra Krishnan-Sarin, Gerald Valentine, Peter I. Jatlow, and Mehmet Sofuoglu. "Modulation of “Protective” Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes." Nicotine & Tobacco Research 22, no. 5 (April 17, 2019): 771–81. http://dx.doi.org/10.1093/ntr/ntz057.
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Abstract Introduction Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products’ reinforcing or aversive actions. Palatable flavors (eg, fruit) may increase appeal through primary reinforcing properties. Menthol’s cooling and anesthetic effects may increase appeal by counteracting nicotine’s aversive effects. Genetics provide a method for modeling individual differences in sensitivity to nicotine’s effects. A common polymorphism, rs16969968, encoded in the α5 nicotinic acetylcholine receptor subunit gene (CHRNA5), is a well-recognized marker for smoking risk and reduces sensitivity to nicotine aversiveness. Methods This pilot study tested how flavors impacted e-cigarette appeal and self-administration. In a single testing day, cigarette smokers (N = 32; 94% menthol-smokers) self-administered e-cigarettes containing e-liquids differing in nicotine level (0 mg/mL, 24 mg/mL) and flavor (unflavored, menthol, fruit-flavored) within directed and ad libitum e-cigarette paradigms. Subjective drug effects, number of puffs, rs16969968 genotype, plasma nicotine, and menthol glucuronide levels were collected. Results Menthol partially ameliorated nicotine aversiveness; fruit did not. In nicotine’s absence, fruit flavor increased self-reported preference and ad libitum use relative to menthol-containing or unflavored e-liquids. Individuals with high-smoking-risk rs16969968 genotype (N = 7) reported greater craving alleviation following directed administration of nicotine-containing e-liquids, showed a trend rating nicotine-containing e-liquids as less harsh, and self-administered more nicotine during ad libitum compared to individuals with low-smoking-risk genotype (N = 23). Conclusions While menthol countered aversiveness of nicotine-containing e-liquids, fruit flavor increased appeal of nicotine-free e-liquids. These preliminary findings suggest menthol and fruit flavor increase e-cigarettes’ appeal through distinct mechanisms. Implications This study provides a detailed characterization of the effects of flavors (unflavored, menthol, fruit), nicotine (0 mg/mL, 24 mg/mL) and their interactions on the subjective drug effects and ad libitum self-administration of e-cigarettes. Genetics were used to assess these effects in higher-smoking-risk (diminished sensitivity to nicotine aversiveness) and lower-risk groups. Findings could inform impact of regulation of flavors or nicotine in e-cigarettes, and their impacts on vulnerable sub-populations.
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Sansone, Luigi, Francesca Milani, Riccardo Fabrizi, Manuel Belli, Mario Cristina, Vincenzo Zagà, Antonio de Iure, Luca Cicconi, Stefano Bonassi, and Patrizia Russo. "Nicotine: From Discovery to Biological Effects." International Journal of Molecular Sciences 24, no. 19 (September 26, 2023): 14570. http://dx.doi.org/10.3390/ijms241914570.
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Nicotine, the primary psychoactive agent in tobacco leaves, has led to the widespread use of tobacco, with over one billion smokers globally. This article provides a historical overview of tobacco and discusses tobacco dependence, as well as the biological effects induced by nicotine on mammalian cells. Nicotine induces various biological effects, such as neoangiogenesis, cell division, and proliferation, and it affects neural and non-neural cells through specific pathways downstream of nicotinic receptors (nAChRs). Specific effects mediated by α7 nAChRs are highlighted. Nicotine is highly addictive and hazardous. Public health initiatives should prioritize combating smoking and its associated risks. Understanding nicotine’s complex biological effects is essential for comprehensive research and informed health policies. While potential links between nicotine and COVID-19 severity warrant further investigation, smoking remains a significant cause of morbidity and mortality globally. Effective public health strategies are vital to promote healthier lifestyles.
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Grieder, Taryn E., Morgane Besson, Geith Maal-Bared, Stéphanie Pons, Uwe Maskos, and Derek van der Kooy. "β2* nAChRs on VTA dopamine and GABA neurons separately mediate nicotine aversion and reward." Proceedings of the National Academy of Sciences 116, no. 51 (November 27, 2019): 25968–73. http://dx.doi.org/10.1073/pnas.1908724116.
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Evidence shows that the neurotransmitter dopamine mediates the rewarding effects of nicotine and other drugs of abuse, while nondopaminergic neural substrates mediate the negative motivational effects. β2* nicotinic acetylcholine receptors (nAChR) are necessary and sufficient for the experience of both nicotine reward and aversion in an intra-VTA (ventral tegmental area) self-administration paradigm. We selectively reexpressed β2* nAChRs in VTA dopamine or VTA γ-amino-butyric acid (GABA) neurons in β2−/−mice to double-dissociate the aversive and rewarding conditioned responses to nicotine in nondependent mice, revealing that β2* nAChRs on VTA dopamine neurons mediate nicotine’s conditioned aversive effects, while β2* nAChRs on VTA GABA neurons mediate the conditioned rewarding effects in place-conditioning paradigms. These results stand in contrast to a purely dopaminergic reward theory, leading to a better understanding of the neurobiology of nicotine motivation and possibly to improved therapeutic treatments for smoking cessation.
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Kedmi, Merav, Arthur L. Beaudet, and Avi Orr-Urtreger. "Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures." Physiological Genomics 17, no. 2 (April 13, 2004): 221–29. http://dx.doi.org/10.1152/physiolgenomics.00202.2003.
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Nicotine, the main addictive component of tobacco, evokes a wide range of dose-dependent behaviors in rodents, and when administrated in high doses, it can induce clonic-tonic seizures. Nicotine acts through the nicotinic acetylcholine receptors (nAChRs). Mutations in the human α4- and the β2-nAChR subunit genes cause autosomal dominant nocturnal frontal lobe epilepsy. Using transgenic mice with mutations in nAChR subunits, it was demonstrated previously that the α4-, α5-, and α7-subunits are involved in nicotine-induced seizures. To examine the possibility that the β4-subunit is also involved in this phenotype, we tested mice with homozygous β4-subunit deficiency. The β4 null mice were remarkably resistant to nicotine-induced seizures compared with wild-type and α5 null mice. We also generated mice with double deficiency of both α5- and β4-nAChR subunits and demonstrated that they were more resistant to nicotine’s convulsant effect than either the α5 or the β4 single mutant mice. In addition, the single α5 mutants and the double α5β4-deficient mice exhibited a significantly shorter latency time to seizure than that of the wild-type mice. Our results thus show that β4-containing nAChRs have a crucial role in the pathogenesis of nicotine-induced seizures. Furthermore, by comparing multiple mutant mice with single and double subunit deficiency, we suggest that nicotinic receptors containing either α5- or β4-subunits are involved in nicotine-induced seizures and that receptors containing both subunits are likely to contribute to this phenomena as well. However, the α5-subunit, but not the β4-subunit, regulates the rate of response to high doses of nicotine.
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Kizawa, Yasuo, Michiko Shinkai, and Issei Takayanagi. "Effects of chronic nicotine treatment on nicotinic receptors in the rabbit urinary bladder." Canadian Journal of Physiology and Pharmacology 68, no. 1 (January 1, 1990): 99–103. http://dx.doi.org/10.1139/y90-015.
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Nicotine induced a phasic contraction in the rabbit urinary bladder. The response was abolished by hexamethonium and partially reduced by atropine and capsaicin. Simultaneous atropine and capsaicin treatment did not abolish the contraction. These findings suggest that the response to nicotine is due to acetylcholine, tachykinins, and unknown mediator release. In contrast, nicotine-induced contraction diminished following the chronic nicotine treatment without a change of its pharmacological properties. These results suggest the possibility that chronic nicotine treatment causes a decrease in nicotinic receptor numbers. Therefore, the binding properties of (−)-[3H]nicotine on rabbit urinary detrusor muscle membrane fractions were studied to evaluate the effects of chronic nicotine treatment on nicotinic receptors. Specific (−)-[3H]nicotine binding reached saturation and Scatchard plots were curvilinear, suggesting the existence of two different affinity sites for (−)-[3H]nicotine. Dissociation constants (KD) and maximum binding sites (Bmax) were KD1 = 4.91 ± 1.88 nM, Bmax1 = 2.42 ± 0.22 fmol/mg protein and KD2 = 263 ± 56 nM, Bmax2 = 25.0 ± 4.3 fmol/mg protein. In urinary bladder membrane fractions from chronic nicotine-treated rabbits, KD and Bmax values were KD1 = 3.96 ± 0.38 nM, Bmax1 = 1.07 ± 0.25 fmol/mg protein and KD2 = 249 ± 12 nM, Bmax2 = 10.8 ± 1.5 fmol/mg protein. Dissociation constants for both sites following chronic nicotine treatment did not change but maximum binding site numbers for both sites significantly decreased (p < 0.05). These results suggest that the decrease in contractile response evoked by nicotine after chronic nicotine treatment in rabbit urinary bladder is due to a decrease in numbers of nicotinic receptors.Key words: nicotine, rabbit urinary bladder, nicotinic receptors.
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Bhanu Prakash G, Rajagopalan Vijayaraghavan, Senthilkumar Sivanesan, and Madhankumar Swaminathan. "A study on the agents that reduces the nicotine induced nicotinic receptor density in wistar rats." International Journal of Research in Pharmaceutical Sciences 12, no. 1 (January 6, 2021): 430–35. http://dx.doi.org/10.26452/ijrps.v12i1.4074.
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The most important substance causing addiction towards cigarette is nicotine. Nicotine abstinence causes withdrawal symptoms in smokers. It is not just nicotine, along with it is the upregulation of nicotinic receptor density (NRD) that leads to addiction. All together makes nicotine deaddiction the most difficult aspect. Nicotine receptor density increases as long as the person is exposed to nicotine. When once the NRD is initiated by nicotine, later though you stop smoking, the increased nicotine receptors create an urge to smoke. Hence the person feels to smoke for satisfying the nicotine receptors. The smokers may attempt to quit smoking but the NRD will create an urge for nicotine again. One cannot completely quit smoking or cannot stop taking nicotine, until the NRD is reduced to normal. In our present study we have studied the effect of citric acid and tyrosine on decreasing nicotinic receptor density. We have induced the nicotinic receptor density to raise and studied the citric acid and tyrosine’s effect in maintaining the NRD closer to normal. The study concludes that citric acid and tyrosine have reduced the NRD significantly. This can control withdrawal symptoms and can stop craving for nicotine and finally can lead to cessation of smoking and from taking nicotine therapy.
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Wongtrakool, Cherry, Susanne Roser-Page, Hilda N. Rivera, and Jesse Roman. "Nicotine alters lung branching morphogenesis through the α7 nicotinic acetylcholine receptor." American Journal of Physiology-Lung Cellular and Molecular Physiology 293, no. 3 (September 2007): L611—L618. http://dx.doi.org/10.1152/ajplung.00038.2007.
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There is abundant epidemiological data linking prenatal environmental tobacco smoke with childhood asthma and wheezing, but the underlying molecular and physiological mechanisms that occur in utero to explain this link remain unelucidated. Several studies suggest that nicotine, which traverses the placenta, is a causative agent. Therefore, we studied the effects of nicotine on lung branching morphogenesis using embryonic murine lung explants. We found that the expression of α7 nicotinic acetylcholine receptors, which mediate many of the biological effects of nicotine, is highest in pseudoglandular stage lungs compared with lungs at later stages. We then studied the effects of nicotine in the explant model and found that nicotine stimulated lung branching in a dose-dependent fashion. α-Bungarotoxin, an antagonist of α7 nicotinic acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS-21, a specific agonist, stimulated branching, thereby mimicking the effects of nicotine. Explants deficient in α7 nicotinic acetylcholine receptors did not respond to nicotine. Nicotine also stimulated the growth of the explant. Altogether, these studies suggest that nicotine stimulates lung branching morphogenesis through α7 nicotinic acetylcholine receptors and may contribute to dysanaptic lung growth, which in turn may predispose the host to airway disease in the postnatal period.
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Intskirveli, Irakli, and Raju Metherate. "Nicotinic neuromodulation in auditory cortex requires MAPK activation in thalamocortical and intracortical circuits." Journal of Neurophysiology 107, no. 10 (May 15, 2012): 2782–93. http://dx.doi.org/10.1152/jn.01129.2011.
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Activation of nicotinic acetylcholine receptors (nAChRs) by systemic nicotine enhances sensory-cognitive function and sensory-evoked cortical responses. Although nAChRs mediate fast neurotransmission at many synapses in the nervous system, nicotinic regulation of cortical processing is neuromodulatory. To explore potential mechanisms of nicotinic neuromodulation, we examined whether intracellular signal transduction involving mitogen-activated protein kinase (MAPK) contributes to regulation of tone-evoked responses in primary auditory cortex (A1) in the mouse. Systemic nicotine enhanced characteristic frequency (CF) tone-evoked current-source density (CSD) profiles in A1, including the shortest-latency (presumed thalamocortical) current sink in layer 4 and longer-latency (presumed intracortical) sinks in layers 2–4, by increasing response amplitudes and decreasing response latencies. Microinjection of the MAPK kinase (MEK) inhibitor U0126 into the thalamus, targeting the auditory thalamocortical pathway, blocked the effect of nicotine on the initial (thalamocortical) CSD component but did not block enhancement of longer-latency (intracortical) responses. Conversely, microinjection of U0126 into supragranular layers of A1 blocked nicotine's effect on intracortical, but not thalamocortical, CSD components. Simultaneously with enhancement of CF-evoked responses, responses to spectrally distant (nonCF) stimuli were reduced, implying nicotinic “sharpening” of frequency receptive fields, an effect also blocked by MEK inhibition. Consistent with these physiological results, acoustic stimulation with nicotine produced immunolabel for activated MAPK in A1, primarily in layer 2/3 cell bodies. Immunolabel was blocked by intracortical microinjection of the nAChR antagonist dihydro-β-erythroidine, but not methyllycaconitine, implicating α4β2*, but not α7, nAChRs. Thus activation of MAPK in functionally distinct forebrain circuits—thalamocortical, local intracortical, and long-range intracortical—underlies nicotinic neuromodulation of A1.
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Washington, Thomas E. "Nicotine's Potential to Protect Brain Cells: The Influence of Nicotine on Alzheimer's Disease Risk in the United States: A Scoping Review." Journal of Medicine, Nursing & Public Health 6, no. 1 (April 25, 2023): 1–12. http://dx.doi.org/10.53819/81018102t4132.
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Nicotine consumption increases brain excitability in a dispersed system of brain areas, such as the frontal cortex, amygdala, cingulate, and frontal lobes, in a dose-dependent manner. Stimulation in these areas is compatible with nicotine's ability to arouse and reinforce behaviour in humans. However, the effects of nicotine consumption on brain cells and the way it modifies them to either inhibit AD or facilitate AD is still unknown, therefore, the current scientific article aimed to address this research gap through analysing prior but latest research studies in this domain. Since there was a need to establish and explore more research regarding the positive impacts of Nicotine on patients with AD, a qualitative research design using secondary data was used to conduct the present scientific evidence. Four published papers within the year range 2017 to 2023 were acquired and thematically evaluated. Mixed findings regarding the impact of nicotine on brain cells and probability of getting AD were found however, there has been no clinical trials or enough empirical studies to support this assumption. Therefore, more research will be needed in the prospective to obtain credible and supporting results. Keywords: Nicotine, Brain cells, nicotinic receptors, Alzheimer’s disease.
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Dhar, S., F. Nagy, J. M. McIntosh, and H. N. Sapru. "Receptor subtypes mediating depressor responses to microinjections of nicotine into medial NTS of the rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 1 (July 1, 2000): R132—R140. http://dx.doi.org/10.1152/ajpregu.2000.279.1.r132.
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Microinjections (50 nl) of nicotine (0.01–10 μM) into the nucleus of the solitary tract (NTS) of adult, urethan-anesthetized, artificially ventilated, male Wistar rats, elicited decreases in blood pressure and heart rate. Prior microinjections of α-bungarotoxin (α-BT) and α-conotoxin ImI (specific toxins for nicotinic receptors containing α7 subunits) elicited a 20–38% reduction in nicotine responses. Similarly, prior microinjections of hexamethonium, mecamylamine, and α-conotoxin AuIB (specific blockers or toxin for nicotinic receptors containing α3β4 subunits) elicited a 47–79% reduction in nicotine responses. Nicotine responses were completely blocked by prior sequential microinjections of α-BT and mecamylamine into the NTS. Complete blockade of excitatory amino acid receptors (EAARs) in the NTS did not attenuate the responses to nicotine. It was concluded that 1) the predominant type of nicotinic receptor in the NTS contains α3β4 subunits, 2) a smaller proportion contains α7 subunits, 3) the presynaptic nicotinic receptors in the NTS do not contribute to nicotine-induced responses, and 4) EAARs in the NTS are not involved in mediating responses to nicotine.
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Huang, Zheng-Gui, Xin Wang, Cory Evans, Allison Gold, Evguenia Bouairi, and David Mendelowitz. "Prenatal Nicotine Exposure Alters the Types of Nicotinic Receptors That Facilitate Excitatory Inputs to Cardiac Vagal Neurons." Journal of Neurophysiology 92, no. 4 (October 2004): 2548–54. http://dx.doi.org/10.1152/jn.00500.2004.
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Nicotinic receptors play an important role in modulating the activity of parasympathetic cardiac vagal neurons in the medulla. Previous work has shown nicotine acts via at least three mechanisms to excite brain stem premotor cardiac vagal neurons. Nicotine evokes a direct increase in holding current and facilitates both the frequency and amplitude of glutamatergic neurotransmission to cardiac vagal neurons. This study tests whether these nicotinic receptor–mediated responses are endogenously active, whether α4β2 and α7 nicotinic receptors are involved, and whether prenatal exposure to nicotine alters the magnitude of these responses and the types of nicotinic receptors involved. Application of neostigmine (10 μM) significantly increased the holding current, amplitude, and frequency of miniature excitatory postsynaptic current (mEPSC) glutamatergic events in cardiac vagal neurons. In unexposed animals, the nicotine-evoked facilitation of mEPSC frequency, but not mEPSC amplitude or holding current, was blocked by α-bungarotoxin (100 nM). Prenatal nicotine exposure significantly exaggerated and altered the types of nicotinic receptors involved in these responses. In prenatal nicotine-exposed animals, α-bungarotoxin only partially reduced the increase in mEPSC frequency. In addition, in prenatal nicotine-exposed animals, the increase in holding current was partially dependent on α-7 subunit–containing nicotinic receptors, in contrast to unexposed animals in which α-bungarotoxin had no effect. These results indicate prenatal nicotine exposure, one of the highest risk factors for sudden infant death syndrome (SIDS), exaggerates the responses and changes the types of nicotinic receptors involved in exciting premotor cardiac vagal neurons. These alterations could be responsible for the pronounced bradycardia that occurs during apnea in SIDS victims.
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Bagdas, Deniz, Laura E. Rupprecht, Eric J. Nunes, Emma Schillinger, Judah J. Immanuel, and Nii A. Addy. "Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats." Nicotine & Tobacco Research 24, no. 5 (November 20, 2021): 753–60. http://dx.doi.org/10.1093/ntr/ntab241.
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Abstract Introduction Tobacco product flavors may change the sensory properties of nicotine, such as taste and olfactory cues, which may alter nicotine reward and aversion and nicotine taking behavior. The hedonic or aversive value of a taste stimulus can be evaluated by examining affective orofacial movements in rodents. Aims and Methods We characterized taste responses to various oral nicotine concentrations using the taste reactivity test in rats. We also evaluated the impact of menthol and benzaldehyde (cherry, almond) flavorants on both ingestive and aversive responses to oral nicotine. Adult Sprague-Dawley rats (n = 5–10 per sex per group) were implanted with intraoral catheters and received 20 infusions (200 µl/ea). Nicotine (1–100 µg/mL) was evaluated in taste reactivity test to determine taste responses to nicotine. Later, the effects of menthol (50 µg/mL) and benzaldehyde (100 µg/mL) on the taste responses to nicotine were determined. Results Nicotine at low concentrations (3 µg/mL in males, 1 µg/mL in females) elicited significantly greater ingestive responses compared with water, whereas higher nicotine concentrations (≥30 µg/mL in males, ≥10 µg/mL in females) elicited significant aversive reactions. Thus, intraoral nicotine induced both hedonic and aversive responses in a concentration- and sex-dependent manner. Females were more sensitive to nicotine’s concentration. The addition of menthol or benzaldehyde significantly increased the hedonic responses to nicotine, and significantly decreased the aversive nicotine responses. Conclusions Oral nicotine induces both hedonic and aversive taste responses, which may represent liking and disliking. Menthol and benzaldehyde can alter the orosensory experience of nicotine, which may influence nicotine’s abuse liability. Implications Our work represents a model to study impact of flavors on oral nicotine liking and disliking responses in rats. Moreover, our findings show that menthol and benzaldehyde alter the orosensory experience of nicotine, suggesting that both could influence nicotine’s abuse liability.
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Boye, Sandra M., and Paul BS Clarke. "Enhancement of haloperidol-induced catalepsy by nicotine: an investigation of possible mechanisms." Canadian Journal of Physiology and Pharmacology 78, no. 11 (November 1, 2000): 882–91. http://dx.doi.org/10.1139/y00-070.
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Nicotine has been reported to potentiate the cataleptic effect of the dopamine receptor antagonist haloperidol in rats. This effect is paradoxical, since nicotine alone tends to increase nigrostriatal dopamine release. In the present experiments, a pro-cataleptic effect of nicotine was confirmed statistically but was small and variable. Three potential mechanisms underlying this effect were investigated. (i) Desensitization of brain nicotinic receptors appears to make little if any contribution to the pro-cataleptic effect of nicotine, insofar as the latter was not mimicked by two centrally active nicotinic antagonists (mecamylamine and chlorisondamine). (ii) Depolarization inactivation resulting from combined treatment with haloperidol and nicotine does not appear to be critical, since the pro-cataleptic effect of nicotine was not enhanced by chronic haloperidol administration, a treatment designed to enhance depolarization inactivation. (iii) The slow emergence and persistence of the acute pro-cataleptic effect of nicotine suggested possible mediation by a nicotine metabolite. However, neither cotinine nor nornicotine, the principal pharmacologically-active metabolites of nicotine, exerted a significant pro-cataleptic effect. In conclusion, the pro-cataleptic effect of nicotine was weak and variable in the present study, and its mechanism remains obscure.Key words: catalepsy, nicotine, haloperidol, Tourette's Syndrome, dopamine, nornicotine.
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Javadi, Parastoo, Ameneh Rezayof, Maryam Sardari, and Zahra Ghasemzadeh. "Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats." Journal of Psychopharmacology 31, no. 7 (May 25, 2017): 945–55. http://dx.doi.org/10.1177/0269881117707745.
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The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5–4 µg/rat) or intra-medial prefrontal cortex (0.2–0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.
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Vigna, Steven R. "Nicotine InhibitsClostridium difficileToxin A-Induced Colitis but Not Ileitis in Rats." International Journal of Inflammation 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/4705065.
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Nicotine is protective in ulcerative colitis but not Crohn’s disease of the small intestine, but little is known about the effects of nicotine onClostridium difficiletoxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4(LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4.
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Abdrakhmanova, Galya R., Shakir AlSharari, Minho Kang, M. Imad Damaj, and Hamid I. Akbarali. "α7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis." American Journal of Physiology-Gastrointestinal and Liver Physiology 299, no. 3 (September 2010): G761—G768. http://dx.doi.org/10.1152/ajpgi.00175.2010.
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Controlled clinical trials of nicotine transdermal patch for treatment of ulcerative colitis have been shown to improve histological and global clinical scores of colitis. Here we report that nicotine (1 μM) suppresses in vitro hyperexcitability of colonic dorsal root ganglia (DRG) (L1–L2) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation. Nicotine gradually reduced regenerative multiple-spike action potentials in colitis mice to a single action potential. Nicotine's effect on hyperexcitability of inflamed neurons was blocked in the presence of an α7-nicotinic acetylcholine receptor (nAChR) antagonist, methyllicaconitine, while choline, the α7-nAChR agonist, induced a similar effect to that of nicotine. Consistent with these findings, nicotine failed to suppress hyperexcitability in colonic DRG neurons from DSS-treated α7 knockout mice. Furthermore, colonic DRG neurons from DSS-treated α7 knockout mice were characterized by lower rheobase (10 ± 5 vs. 77 ± 13 pA, respectively) and current threshold (28 ± 4 vs. 103 ± 8 pA, respectively) levels than DSS-treated C57BL/J6 mice. An interesting observation of this study is that 8 of 12 colonic DRG (L1–L2) neurons from control α7 knockout mice exhibited multiple-spike action potential firing while no wild-type neurons did. Overall, our findings suggest that nicotine at low 1 μM concentration suppresses in vitro hyperexcitability of inflamed colonic DRG neurons in a mouse model of acute colonic inflammation via activation of α7-nAChRs.
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Pan, Yiou, Pengjun Xu, Xiaochun Zeng, Xuemei Liu, and Qingli Shang. "Characterization of UDP-Glucuronosyltransferases and the Potential Contribution to Nicotine Tolerance in Myzus persicae." International Journal of Molecular Sciences 20, no. 15 (July 25, 2019): 3637. http://dx.doi.org/10.3390/ijms20153637.
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Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are major phase II detoxification enzymes involved in glycosylation of lipophilic endobiotics and xenobiotics, including phytoalexins. Nicotine, one of the most abundant secondary plant metabolites in tobacco, is highly toxic to herbivorous insects. Plant-herbivore competition is the major impetus for the evolution of large superfamilies of UGTs and other detoxification enzymes. However, UGT functions in green peach aphid (Myzus persicae) adaptation are unknown. In this study, we show that UGT inhibitors (sulfinpyrazone and 5-nitrouracil) significantly increased nicotine toxicity in M. persicae nicotianae, suggesting that UGTs may be involved in nicotine tolerance. In total, 101 UGT transcripts identified in the M. persicae genome/transcriptome were renamed according to the UGT Nomenclature Committee guidelines and grouped into 11 families, UGT329, UGT330, UGT339, UGT341–UGT345, and UGT348–UGT350, with UGT344 containing the most (57). Ten UGTs (UGT330A3, UGT339A2, UGT341A6, UGT342B3, UGT343C3, UGT344D5, UGT344D8, UGT348A3, UGT349A3, and UGT350A3) were highly expressed in M. persicae nicotianae compared to M. persicae sensu stricto. Knockdown of four UGTs (UGT330A3, UGT344D5, UGT348A3, and UGT349A3) significantly increased M. persicae nicotianae sensitivity to nicotine, suggesting that UGT expression in this subspecies may be associated with nicotine tolerance and thus host adaptation. This study reveals possible UGTs relevant to nicotine adaptation in tobacco-consuming M. persicae nicotianae, and the findings will facilitate further validation of the roles of these UGTs in nicotine tolerance.
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Smucny, Jason, and Jason R. Tregellas. "Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging." Journal of Psychopharmacology 31, no. 7 (April 26, 2017): 801–11. http://dx.doi.org/10.1177/0269881117705071.
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Patients with schizophrenia self-administer nicotine at rates higher than is self-administered for any other psychiatric illness. Although the reasons are unclear, one hypothesis suggests that nicotine is a form of ‘self-medication’ in order to restore normal levels of nicotinic signaling and target abnormalities in neuronal function associated with cognitive processes. This brief review discusses evidence from neurophysiological and neuroimaging studies in schizophrenia patients that nicotinic agonists may effectively target dysfunctional neuronal circuits in the illness. Evidence suggests that nicotine significantly modulates a number of these circuits, although relatively few studies have used modern neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to examine the effects of nicotinic drugs on disease-related neurobiology. The neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain a priority for psychiatry research.
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Xu, Shuqing, Thomas Brockmöller, Aura Navarro-Quezada, Heiner Kuhl, Klaus Gase, Zhihao Ling, Wenwu Zhou, et al. "Wild tobacco genomes reveal the evolution of nicotine biosynthesis." Proceedings of the National Academy of Sciences 114, no. 23 (May 23, 2017): 6133–38. http://dx.doi.org/10.1073/pnas.1700073114.
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Nicotine, the signature alkaloid of Nicotiana species responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos, Nicotiana attenuata (2.5 Gb) and Nicotiana obtusifolia (1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole-genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated these Nicotiana genomes, promoted expression divergences among duplicated genes, and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinamide adenine dinucleotide (NAD) pathways. In contrast to the duplication of the polyamine pathway that is shared among several solanaceous genera producing polyamine-derived tropane alkaloids, we found that lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor that activates the expression of all nicotine biosynthetic genes resulted in the innovative and efficient production of nicotine in the genus Nicotiana. Transcription factor binding motifs derived from TEs may have contributed to the coexpression of nicotine biosynthetic pathway genes and coordinated the metabolic flux. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.
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Wang, Rui, and Zunzhe Wang. "Three different vasoactive responses of rat tail artery to nicotine." Canadian Journal of Physiology and Pharmacology 78, no. 1 (December 22, 1999): 20–28. http://dx.doi.org/10.1139/y99-114.
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The vasoactive effects of nicotine on isolated rat tail artery tissues were studied. Nicotine transiently contracted rat tail artery tissues (EC50, 55.6 ± 2 µM) in an extracellular Ca2+ dependent and endothelium-independent fashion. The blockade of alpha1-adrenoceptors, but not alpha2-adrenoceptors or P2X purinoceptors, inhibited the nicotine-induced contraction by 38 ± 7% (p < 0.05). Nicotine (1 mM) depolarized membrane by 13 ± 3 mV, but did not affect L-type Ca2+ channel currents, of the isolated rat tail artery smooth muscle cells. The phenylephrine-precontracted tail artery tissues were relaxed by nicotine (EC50, 0.90 ± 0.31 mM), which was significantly inhibited after the blockade of nicotinic receptors. Simultaneous removal of phenylephrine and nicotine, after a complete relaxation of the phenylephrine-precontracted tail artery strips was achieved by nicotine at accumulated concentrations (>=10 mM), triggered a Ca2+-dependent rebound long-lasting vasoconstriction (n = 20). This rebound contraction was abolished in the absence of calcium or in the presence of tetracaine in the bath solution. Pretreatment of vascular tissues with a nicotinic receptor antagonist did not affect the nicotine-induced vasoconstriction or nicotine withdrawal induced rebound contraction. The elucidation of the triphasic vascular effects of nicotine and the underlying mechanisms is important for a better understanding of the complex vascular actions of nicotine.Key words: nicotine, smokeless tobacco, vascular smooth muscles, contraction, relaxation.
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Sharma, Geeta, and Sukumar Vijayaraghavan. "Nicotinic Receptors: Role in Addiction and Other Disorders of the Brain." Substance Abuse: Research and Treatment 1 (January 2008): 117822180800100. http://dx.doi.org/10.1177/117822180800100005.
Full textAbstract:
Nicotine, the addictive component of cigarette smoke has profound effects on the brain. Activation of its receptors by nicotine has complex consequences for network activity throughout the brain, potentially contributing to the addictive property of the drug. Nicotinic receptors have been implicated in psychiatric illnesses like schizophrenia and are also neuroprotective, potentially beneficial for neurodegenerative diseases. These effects of nicotine serve to emphasize the multifarious roles the drug, acting through multiple nicotinic acetylcholine receptor subtypes. The findings also remind us of the complexity of signaling mechanisms and stress the risks of unintended consequences of drugs designed to combat nicotine addiction.
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Wollman, Lila Buls, Richard B. Levine, and Ralph F. Fregosi. "Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats." Journal of Neurophysiology 120, no. 3 (September 1, 2018): 1135–42. http://dx.doi.org/10.1152/jn.00600.2017.
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We tested the hypothesis that nicotine exposure in utero and after birth [developmental nicotine exposure (DNE)] disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brain stem slices from 1- to 5-day-old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine (ACh) receptors with nicotine (i.e., an acute nicotine challenge). Under baseline conditions, there were no significant effects of DNE on the amplitude or frequency of either sIPSCs or mIPSCs. In addition, DNE did not alter the magnitude of the whole cell current evoked by bath application of glycine, consistent with an absence of change in postsynaptic glycine-mediated conductance. An acute nicotine challenge (bath application of 0.5 μM nicotine) increased sIPSC frequency in the DNE cells, but not control cells. In contrast, nicotine challenge did not change mIPSC frequency in either control or DNE cells. In addition, there were no significant changes in the amplitude of either sIPSCs or mIPSCs in response to nicotine challenge. The increased frequency of sIPSCs in response to an acute nicotine challenge in DNE cells reflects an enhancement of action potential-mediated input from glycinergic interneurons to hypoglossal motoneurons. This could lead to more intense inhibition of hypoglossal motoneurons in response to exogenous nicotine or endogenous ACh. The former would occur with smoking or e-cigarette use while the latter occurs with changes in sleep state and with hypercapnia. NEW & NOTEWORTHY Here we show that perinatal nicotine exposure does not impact baseline glycinergic neurotransmission to hypoglossal motoneurons but enhances glycinergic inputs to hypoglossal motoneurons in response to activation of nicotinic acetylcholine (ACh) receptors with acute nicotine. Given that ACh is the endogenous ligand for nicotinic ACh receptors, the latter reveals a potential mechanism whereby perinatal nicotine exposure alters motor function under conditions where ACh release increases, such as the transition from non-rapid-eye movement to rapid-eye movement sleep, and during hypercapnia.
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Hawkins, Brian T., Richard D. Egleton, and Thomas P. Davis. "Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors." American Journal of Physiology-Heart and Circulatory Physiology 289, no. 1 (July 2005): H212—H219. http://dx.doi.org/10.1152/ajpheart.01210.2004.
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Nicotine increases the permeability of the blood-brain barrier in vivo. This implies a possible role for nicotinic acetylcholine receptors in the regulation of cerebral microvascular permeability. Expression of nicotinic acetylcholine receptor subunits in cerebral microvessels was investigated with immunofluorescence microscopy. Positive immunoreactivity was found for receptor subunits α3, α5, α7, and β2, but not subunits α4, β3, or β4. Blood-brain barrier permeability was assessed via in situ brain perfusion with [14C]sucrose. Nicotine increased the rate of sucrose entry into the brain from 0.3 ± 0.1 to 1.1 ± 0.2 μl·g−1·min−1, as previously described. This nicotine-induced increase in blood-brain barrier permeability was significantly attenuated by both the blood-brain barrier-permeant nicotinic antagonist mecamylamine and the blood-brain barrier-impermeant nicotinic antagonist hexamethonium to 0.5 ± 0.2 and 0.3 ± 0.2 μl·g−1·min−1, respectively. These data suggest that nicotinic acetylcholine receptors expressed on the cerebral microvascular endothelium mediate nicotine-induced changes in blood-brain barrier permeability.
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Jinks, Steven L., and E. Carstens. "Activation of Spinal Wide Dynamic Range Neurons by Intracutaneous Microinjection of Nicotine." Journal of Neurophysiology 82, no. 6 (December 1, 1999): 3046–55. http://dx.doi.org/10.1152/jn.1999.82.6.3046.
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Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 μl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01–10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested ( n = 30) also responded to ic histamine (1 μl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40–60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.
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Simons, Christopher T., Yves Boucher, Mirela Iodi Carstens, and E. Carstens. "Nicotine Suppression of Gustatory Responses of Neurons in the Nucleus of the Solitary Tract." Journal of Neurophysiology 96, no. 4 (October 2006): 1877–86. http://dx.doi.org/10.1152/jn.00345.2006.
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This study investigated effects of nicotine applied to the tongue surface on responses of gustatory neurons in the nucleus of the solitary tract (NTS) in rats. In pentobarbital-anesthetized rats, single-unit recordings were made from NTS units responsive to one or more tastants (sucrose, NaCl, citric acid, monosodium glutamate, quinine). Application of nicotine (0.87, 8.7, or 600 mM) excited gustatory NTS units and significantly attenuated NTS unit responses to their preferred tastant in a dose-dependent manner. The depressant effect of nicotine was equivalent regardless of which tastant best excited the NTS unit. Nicotinic excitation of NTS units and depression of their tastant-evoked responses were both significantly attenuated by the nicotinic antagonist mecamylamine, which itself did not excite NTS units. In rats with bilateral trigeminal ganglionectomy, nicotine still excited nearly all NTS units but no longer depressed tastant-evoked responses. Nicotine did not elicit plasma extravasation when applied to the tongue. The results indicate that nicotine directly excites NTS units by gustatory nerves and inhibits their tastant-evoked responses by a nicotinic acetylcholine receptor-mediated excitation of trigeminal afferents that inhibit NTS units centrally.
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Huang, Z. G., K. J. S. Griffioen, X. Wang, O. Dergacheva, H. Kamendi, C. Gorini, and D. Mendelowitz. "Nicotinic Receptor Activation Occludes Purinergic Control of Central Cardiorespiratory Network Responses to Hypoxia/Hypercapnia." Journal of Neurophysiology 98, no. 4 (October 2007): 2429–38. http://dx.doi.org/10.1152/jn.00448.2007.
Full textAbstract:
Prenatal nicotine exposure alters the cardiorespiratory network responses to hypoxia/hypercapnia; however the mechanism(s) responsible for these cardiorespiratory network responses and their alteration by prenatal nicotine exposure are unknown. We used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and excitatory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Respiratory related increases in glutamatergic neurotransmission only occurred on recovery from hypoxia/hypercapnia in unexposed animals. These responses were not altered by nicotinic antagonists but were mediated in part by activation of P2 purinergic receptors. Prenatal nicotine exposure transformed central cardiorespiratory responses to hypoxia/hypercapnia; CVNs received a respiratory related glutamatergic neurotransmission during periods of hypoxia and hypercapnia, whereas increases in glutamatergic neurotransmission during recovery were absent. The excitatory neurotransmission to CVNs during hypoxia/hypercapnia in prenatal nicotine-exposed animals were wholly dependent on nicotinic receptor activation. In the presence of nicotinic antagonists, the responses in prenatal nicotine animals reverted to the pattern of responses in unexposed animals in which an increase in glutamatergic neurotransmission occurred not during but only on recovery from hypoxia/hypercapnia, and this recruited excitatory pathway was blocked by P2 receptor antagonists. These data identify a new functional role for purinergic receptors in the cardiorespiratory responses to hypoxia/hypercapnia and their role in occluding nicotinic receptor activation with prenatal nicotine exposure.
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Lapner, K. N., C. J. Montpetit, and S. F. Perry. "Desensitisation of chromaffin cell nicotinic receptors does not impede catecholamine secretion during acute hypoxia in rainbow trout (Oncorhynchus mykiss)." Journal of Experimental Biology 203, no. 10 (May 15, 2000): 1589–97. http://dx.doi.org/10.1242/jeb.203.10.1589.
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Experiments were performed on adult rainbow trout (Oncorhynchus mykiss) in vivo using chronically cannulated fish and in situ using a perfused posterior cardinal vein preparation (i) to characterise the desensitisation of chromaffin cell nicotinic receptors and (ii) to assess the ability of fish to secrete catecholamines during acute hypoxia with or without functional nicotinic receptors. Intra-arterial injection of nicotine (6.0×10(−)(7)mol kg(−)(1)) caused a rapid increase in plasma adrenaline and noradrenaline levels; the magnitude of this response was unaffected by an injection of nicotine given 60 min earlier. Evidence for nicotinic receptor desensitisation, however, was provided during continuous intravenous infusion of nicotine (1.3×10(−)(5)mol kg(−)(1)h(−)(1)) in which plasma catecholamine levels increased initially but then returned to baseline levels. To ensure that the decline in circulating catecholamine concentrations during continuous nicotine infusion was not related to changes in storage levels or altered rates of degradation/clearance, in situ posterior cardinal vein preparations were derived from fish previously experiencing 60 min of saline or nicotine infusion. Confirmation of nicotinic receptor desensitisation was provided by demonstrating that the preparations derived from nicotine-infused fish were unresponsive to nicotine (10(−)(5)mol l(−)(1)), yet remained responsive to angiotensin II (500 pmol kg(−)(1)). The in situ experiments demonstrated that desensitisation of the nicotinic receptor occurred within 5 min of receptor stimulation and that resensitisation was established 40 min later. The ability to elevate plasma catecholamine levels during acute hypoxia (40–45 mmHg; 5.3-6.0 kPa) was not impaired in fish experiencing nicotinic receptor desensitisation. Indeed, peak plasma adrenaline levels were significantly higher in the desensitised fish during hypoxia than in controls (263+/−86 versus 69+/−26 nmol l(−)(1); means +/− s.e.m., N=6-9). Thus, the results of the present study demonstrate that activation of preganglionic sympathetic cholinergic nerve fibres and the resultant stimulation of nicotinic receptors is not the sole mechanism for eliciting catecholamine secretion during hypoxia.
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Beckel, Jonathan M., Anthony Kanai, Sun-Ju Lee, William C. de Groat, and Lori A. Birder. "Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells." American Journal of Physiology-Renal Physiology 290, no. 1 (January 2006): F103—F110. http://dx.doi.org/10.1152/ajprenal.00098.2005.
Full textAbstract:
Although nicotinic acetylcholine receptors in both the central and peripheral nervous systems play a prominent role in the control of urinary bladder function, little is known regarding expression or function of nicotinic receptors in the bladder epithelium, or urothelium. Nicotinic receptors have been described in epithelial cells lining the upper gastrointestinal tract, respiratory tract, and the skin. Thus the present study examined the expression and functionality of nicotinic receptors in the urothelium, as well as the effects of stimulation of nicotinic receptors on the micturition reflex. mRNA for the α3, α5, α7, β3, and β4 nicotinic subunits was identified in rat urothelial cells using RT-PCR. Western blotting also confirmed urothelial expression of the α3- and α7-subunits. Application of nicotine (50 nM) to cultured rat urothelial cells elicited an increase in intracellular Ca2+ concentration, indicating that at least some of the subunits form functional channels. These effects were blocked by the application of the nicotinic antagonist hexamethonium. During in vivo bladder cystometrograms in urethane-anesthetized rats, intravesical administration of nicotine, choline, or the antagonists methyllycaconitine citrate and hexamethonium elicited changes in voiding parameters. Intravesical nicotine (50 nM, 1 μM) increased the intercontraction interval. Intravesical choline (1–100 μM) also affected bladder reflexes similarly, suggesting that α7 nicotinic receptors mediate this effect. Intravesical administration of hexamethonium (1–100 μM) potentiated the nicotine-induced changes in bladder reflexes. Methyllycaconitine citrate, a specific α7-receptor antagonist, prevented nicotine-, choline-, and hexamethonium-induced bladder inhibition. These results are the first indication that stimulation of nonneuronal nicotinic receptors in the bladder can affect micturition.
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Singh, Sandeep, Smitha Pillai, and Srikumar Chellappan. "Nicotinic Acetylcholine Receptor Signaling in Tumor Growth and Metastasis." Journal of Oncology 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/456743.
Full textAbstract:
Cigarette smoking is highly correlated with the onset of a variety of human cancers, and continued smoking is known to abrogate the beneficial effects of cancer therapy. While tobacco smoke contains hundreds of molecules that are known carcinogens, nicotine, the main addictive component of tobacco smoke, is not carcinogenic. At the same time, nicotine has been shown to promote cell proliferation, angiogenesis, and epithelial-mesenchymal transition, leading to enhanced tumor growth and metastasis. These effects of nicotine are mediated through the nicotinic acetylcholine receptors that are expressed on a variety of neuronal and nonneuronal cells. Specific signal transduction cascades that emanate from different nAChR subunits or subunit combinations facilitate the proliferative and prosurvival functions of nicotine. Nicotinic acetylcholine receptors appear to stimulate many downstream signaling cascades induced by growth factors and mitogens. It has been suggested that antagonists of nAChR signaling might have antitumor effects and might open new avenues for combating tobacco-related cancer. This paper examines the historical data connecting nicotine tumor progression and the recent efforts to target the nicotinic acetylcholine receptors to combat cancer.
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Taylor, George, Carl Bassi, and Juergen Weiss. "Limits of learning enhancements with nicotine in old male rats." Acta Neurobiologiae Experimentalis 65, no. 2 (June 30, 2005): 125–36. http://dx.doi.org/10.55782/ane-2005-1545.
Full textAbstract:
Findings with young adult humans and animal models suggest that nicotine may serve both neuroprotective and cognition enhancing roles in old animals. A pair of experiments was conducted to examine drug-induced modification of the cholinergic nicotinic receptor subtype on rates of learning by young and aged rats. In experiment I males (4-7 months or 20-25 months old) were administered nicotine (0.0, 0.3 or 0.7 mg/kg injected s.c. daily) and tested in both a T-maze non-spatial discrimination paradigm and a hole board spatial task. Nicotine failed to improve acquisition by young animals on either task. Nicotine also failed to improve non-spatial learning by old animals. However, both dosages of nicotine improved performance by the old males in the spatial paradigm. In experiment II, a 5-choice serial discrimination paradigm designed to better evaluate visual attention and spatial working memory in aging was used. Groups of old male rats were administered nicotine or mecamylamine (2 or 8 mg/kg), an antagonist of the nicotinic cholinergic receptor. Results were that the 0.3 mg nicotine group learned the task fastest and achieved the highest learning asymptote. Both learning rates and final levels of performance were worst in the 8 mg mecamylamine group. However, the 2 mg mecamylamine rats were the equals of the control group and both reached a higher asymptote than the 0.7 mg nicotine group. These data suggest that healthy old animals can accrue benefits from nicotinic activation but that the benefits are complex, being limited to certain dosages and to specific cognitive skills.
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CATTANEO, G. Maria, Fabio D'ATRI, and M. Lucia VICENTINI. "Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells." Biochemical Journal 328, no. 2 (December 1, 1997): 499–503. http://dx.doi.org/10.1042/bj3280499.
Full textAbstract:
We have previously reported that nicotine stimulates cell proliferation of three small-cell lung carcinoma (SCLC) cell lines by activating nicotinic receptors of the neuronal type. Here we report that, in the GLC-8 SCLC cell line, nicotine stimulates mitogen-activated protein (MAP) kinase activity in a concentration- and time-dependent manner (ED50 = 10 nM). The nicotine effect was antagonized by mecamylamine, an antagonist specific for neuronal nicotinic receptors. The absence of extracellular Ca2+, or pretreatment with pertussis toxin or the tyrosine kinase inhibitor genistein inhibited the action of nicotine on MAP kinase. Moreover, supernatants from nicotine-stimulated cells transferred to cells pretreated with mecamylamine were still capable of activating MAP kinase. On the other hand, the same supernatants transferred to cells pretreated with mecamylamine and pertussis toxin or genistein failed to activate MAP kinase. These findings suggest that nicotine elicits its stimulatory effect on MAP kinase in SCLC cells indirectly by inducing the production and/or release of a factor which then acts via a pertussis toxin- and tyrosine kinase-sensitive route.
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Duncan, Jhodie R., Marianne Garland, Michael M. Myers, William P. Fifer, May Yang, Hannah C. Kinney, and Raymond I. Stark. "Prenatal nicotine-exposure alters fetal autonomic activity and medullary neurotransmitter receptors: implications for sudden infant death syndrome." Journal of Applied Physiology 107, no. 5 (November 2009): 1579–90. http://dx.doi.org/10.1152/japplphysiol.91629.2008.
Full textAbstract:
During pregnancy, exposure to nicotine and other compounds in cigarette smoke increases the risk of the sudden infant death syndrome (SIDS) two- to fivefold. Serotonergic (5-HT) abnormalities are found, in infants who die of SIDS, in regions of the medulla oblongata known to modulate cardiorespiratory function. Using a baboon model, we tested the hypothesis that prenatal exposure to nicotine alters 5-HT receptor and/or transporter binding in the fetal medullary 5-HT system in association with cardiorespiratory dysfunction. At 87 (mean) days gestation (dg), mothers were continuously infused with saline ( n = 5) or nicotine ( n = 5) at 0.5 mg/h. Fetuses were surgically instrumented at 129 dg for cardiorespiratory monitoring. Cesarean section delivery and retrieval of fetal medulla were performed at 161 (mean) dg for autoradiographic analyses of nicotinic and 5-HT receptor and transporter binding. In nicotine-exposed fetuses, high-frequency heart rate variability was increased 55%, possibly reflecting increases in the parasympathetic control of heart rate. This effect was more pronounced with greater levels of fetal breathing and age. These changes in heart rate variability were associated with increased 5-HT1A receptor binding in the raphé obscurus ( P = 0.04) and increased nicotinic receptor binding in the raphé obscurus and vagal complex ( P < 0.05) in the nicotine-exposed animals compared with controls ( n = 6). The shift in autonomic balance in the fetal primate toward parasympathetic predominance with chronic exposure to nicotine may be related, in part, to abnormal 5-HT-nicotine alterations in the raphé obscurus. Thus increased risk for SIDS due to maternal smoking may be partly related to the effects of nicotine on 5-HT and/or nicotinic receptors.
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Ene, Corina-Daniela, Mircea Penescu, Ilinca Nicolae, and Emanoil Ceauşu. "Anti-inflammatory effects of nicotine." Romanian Journal of Infectious Diseases 18, no. 1 (March 31, 2015): 5–12. http://dx.doi.org/10.37897/rjid.2015.1.1.
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A number of epidemiological and experimental data have shown that nicotine stimulates anti-inflammatory response in extraneuronal tissues, response mediated by homopentameric nicotinic receptors, 7nAChR- alpha. The receptors are located mainly on immune and inflammatory cells. These pharmacological mechanisms, through which inflammatory process could be adjusted is the use of selective nicotinic agonists and antagonists, called anti-inflammatory. Treatment with nicotine initiates a series of intracellular events associated with stimulation of several signaling pathways: NFkB, JAK/STAT, MyD88/TLRs, MAPKs/ERKs. Knowledge of anti-inflammatory mechanisms mediated by alpha7nAChR is useful for valuing the therapeutic potential of nicotine in regulating the inflammatory response in certain pathological processes.
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Leventhal, Adam M., Tyler B. Mason, Sam N. Cwalina, Lauren Whitted, Marissa Anderson, and Carly Callahan. "Flavor and Nicotine Effects on E-cigarette Appeal in Young Adults: Moderation by Reason for Vaping." American Journal of Health Behavior 44, no. 5 (September 1, 2020): 732–43. http://dx.doi.org/10.5993/ajhb.44.5.15.
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Objectives: Effective regulations that reduce nicotine vaping among young adult dual (combustible and e-cigarette) users may differ depending on whether e-cigarettes are used for helping with smoking cessation. This laboratory experiment examined flavor and nicotine effects on e-cigarette product appeal among young adult dual users, stratified by reported use of e-cigarettes to quit smoking. Methods: Dual users aged 18-35 years that did (N = 31) or did not (N = 22) report vaping for the purpose of quitting smoking puffed e-cigarette solutions varied by a flavor (fruit, menthol, tobacco) and nicotine (nicotine-containing [6 mg/mL], nicotine-free) with-in-participant design. After puffing each solution, participants rated appeal. Results: In main effect analyses, non-tobacco (vs tobacco) flavors increased appeal and nicotine-containing (vs nicotine free) solutions reduced appeal similarly in dual users who did and did not vape to quit smoking. Interaction analyses found non-significant trend evidence that fruit and menthol flavors suppressed nicotine's appeal-reducing effects more powerfully in those that did not vape to quit smoking (flavor × nicotine × vape to quit smoking, ps = .05-.06). Conclusions: Non-tobacco flavors might increase e-cigarette product appeal in young adult dual users overall and disproportionately suppress nicotine's appeal-reducing effects in those that vape for purposes other than assisting with smoking cessation.
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Papapostolou, Irida, Daniela Ross-Kaschitza, Florian Bochen, Christine Peinelt, and Maria Constanza Maldifassi. "Contribution of the α5 nAChR Subunit and α5SNP to Nicotine-Induced Proliferation and Migration of Human Cancer Cells." Cells 12, no. 15 (August 4, 2023): 2000. http://dx.doi.org/10.3390/cells12152000.
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Nicotine in tobacco is known to induce tumor-promoting effects and cause chemotherapy resistance through the activation of nicotinic acetylcholine receptors (nAChRs). Many studies have associated the α5 nicotinic receptor subunit (α5), and a specific polymorphism in this subunit, with (i) nicotine administration, (ii) nicotine dependence, and (iii) lung cancer. The α5 gene CHRNA5 mRNA is upregulated in several types of cancer, including lung, prostate, colorectal, and stomach cancer, and cancer severity is correlated with smoking. In this study, we investigate the contribution of α5 in the nicotine-induced cancer hallmark functions proliferation and migration, in breast, colon, and prostate cancer cells. Nine human cell lines from different origins were used to determine nAChR subunit expression levels. Then, selected breast (MCF7), colon (SW480), and prostate (DU145) cancer cell lines were used to investigate the nicotine-induced effects mediated by α5. Using pharmacological and siRNA-based experiments, we show that α5 is essential for nicotine-induced proliferation and migration. Additionally, upon downregulation of α5, nicotine-promoted expression of EMT markers and immune regulatory proteins was impaired. Moreover, the α5 polymorphism D398N (α5SNP) caused a basal increase in proliferation and migration in the DU145 cell line, and the effect was mediated through G-protein signaling. Taken together, our results indicate that nicotine-induced cancer cell proliferation and migration are mediated via α5, adding to the characterization of α5 as a putative therapeutical target.
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Liu, L., W. Zhu, Z. S. Zhang, T. Yang, A. Grant, G. Oxford, and S. A. Simon. "Nicotine Inhibits Voltage-Dependent Sodium Channels and Sensitizes Vanilloid Receptors." Journal of Neurophysiology 91, no. 4 (April 2004): 1482–91. http://dx.doi.org/10.1152/jn.00922.2003.
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Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (∼41°C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.
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Kanniah, Guna, and Rishi Kumar. "A selective literature review exploring the role of the nicotinic system in schizophrenia." General Psychiatry 36, no. 2 (March 2023): e100756. http://dx.doi.org/10.1136/gpsych-2022-100756.
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Nicotine use is more prevalent in patients with psychiatric disorders, especially those diagnosed with psychotic illnesses. Previously, this higher prevalence has been partially attributed to the potential ameliorative effects of nicotine on symptom severity and cognitive impairment. Some healthcare professionals and patients perceive there is a beneficial effect of nicotine on mental health. Emerging data show that the harm associated with nicotine in the population of patients with mental health conditions outweighs any potential benefit. This paper will review the evidence surrounding the nicotinic system and schizophrenia, with a focus on any causality between nicotine and psychosis.
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Alkire, Michael T., Jayme R. McReynolds, Emily L. Hahn, and Akash N. Trivedi. "Thalamic Microinjection of Nicotine Reverses Sevoflurane-induced Loss of Righting Reflex in the Rat." Anesthesiology 107, no. 2 (August 1, 2007): 264–72. http://dx.doi.org/10.1097/01.anes.0000270741.33766.24.
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Background Neuronal nicotinic acetylcholine receptors are both potently inhibited by anesthetics and densely expressed in the thalamus. Brain imaging shows that thalamic activity suppression accompanies anesthetic-induced unconsciousness. Therefore, anesthetic-induced unconsciousness may involve direct antagonism of thalamic nicotinic receptors. The authors test this by separately attempting to block or enhance anesthetic-induced loss of righting in rats using intrathalamic microinjections of nicotine or its antagonist. Methods Rats were implanted with a cannula aimed at the thalamus or control locations. A week later, loss of righting was induced using sevoflurane (1.4 +/- 0.2%). A dose-parameter study (n = 35) first identified an optimal intrathalamic nicotine dose associated with arousal. Subsequently, this dose was used to pinpoint the thalamic site mediating the arousal response (n = 107). Finally, sevoflurane righting dose and response specificity were assessed after blocking nicotinic channels with intrathalamic mecamylamine pretreatment (n = 8) before nicotine challenge. Results Nicotine (150 microg/0.5 microl over 1 min) was the optimal arousal dose, because lower doses (75 microg) were ineffective and higher doses (300 microg) often caused seizures. Nicotine temporarily restored righting and mobility in animals when microinjections involved the central medial thalamus (P < 0.0001, chi-square). Righting occurred despite continued sevoflurane administration. Intrathalamic mecamylamine pretreatment did not lower the sevoflurane dose associated with loss of righting, but prevented the nicotine arousal response. Conclusions The reversal of unconsciousness found here with intrathalamic microinfusion of nicotine suggests that suppression of the midline thalamic cholinergic arousal system is part of the mechanism by which anesthetics produce unconsciousness.
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Lian, Jie, De Ji Wang, and Jun Ming Xie. "Data Mining of Nicotine Demethylase Genes in Modern Tobacoo." Advanced Materials Research 787 (September 2013): 356–60. http://dx.doi.org/10.4028/www.scientific.net/amr.787.356.
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The predominant pyridine alkaloid in modern tobacco (Nicotiana tabacum) is Nicotine. However, with the existence of a class of Nicotine demethylases, a large proportion of Nicotine will be converted into Nornicotine during leaf senescence. Identification of Nicotine demethylases in modern tobacco is important, since Nornicotine will be nitrosated into N'-nitrosonornicotine (NNN), which exhibit carcinogenic properties in laboratory animals and is harmful for human heath. Although many efforts have been performed to identified, no comprehensive analysis was carried out for the subfamily of Nicotine demethylases. In this work, we performed a phylogenetic and comparative analysis for Nicotine demethylases with their highly homologs. A single and conserved mutation of W->C will prohibit the activity of Nicotine demethylases. Thus, the proportion of Nornicotine could be dramatically decreased if all Nicotine demethylase were single mutated by transgenic manipulation. Our results provide an insightful and solid foundation for further experimental design.
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Calarco, Cali A., and Marina R. Picciotto. "Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake." Nicotine & Tobacco Research 22, no. 2 (January 25, 2019): 152–63. http://dx.doi.org/10.1093/ntr/ntz010.
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Abstract Despite health risks associated with smoking, up to 20% of the US population persist in this behavior; many smoke to control body weight or appetite, and fear of post-cessation weight gain can motivate continued smoking. Nicotine and tobacco use is associated with lower body weight, and cessation yields an average weight gain of about 4 kg, which is thought to reflect a return to the body weight of a typical nonsmoker. Nicotine replacement therapies can delay this weight gain but do not prevent it altogether, and the underlying mechanism for how nicotine is able to reduce weight is not fully understood. In rodent models, nicotine reduces weight gain, reduces food consumption, and alters energy expenditure, but these effects vary with duration and route of nicotine administration. Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide and anorexigenic proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (ARC). Manipulation of nAChR subunit expression within the ARC can block the ability of nicotine and the nicotinic agonist cytisine from decreasing food intake; however, it is unknown exactly how this reduces food intake. This review summarizes the clinical and preclinical work on nicotine, food intake, and weight gain, then explores the feeding circuitry of the ARC and how it is regulated by nicotine. Finally, we propose a novel hypothesis for how nicotine acts on this hypothalamic circuit to reduce food intake. Implications: This review provides a comprehensive and updated summary of the clinical and preclinical work examining nicotine and food intake, as well as a summary of recent work examining feeding circuits of the hypothalamus. Synthesis of these two topics has led to new understanding of how nAChR signaling regulates food intake circuits in the hypothalamus.
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Perry, Robin N., Hera E. Schlagintweit, Christine Darredeau, Carl Helmick, Aaron J. Newman, Kimberley P. Good, and Sean P. Barrett. "The impacts of actual and perceived nicotine administration on insula functional connectivity with the anterior cingulate cortex and nucleus accumbens." Journal of Psychopharmacology 33, no. 12 (September 23, 2019): 1600–1609. http://dx.doi.org/10.1177/0269881119872205.
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Background: Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine’s effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine’s pharmacological actions to such effects requires clarification. Aims: The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses. Methods: Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration. Results: Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula. Conclusions: Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.
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Whitton, Alexis E., Norka E. Rabinovich, John D. Lindt, Michele L. Pergadia, Diego A. Pizzagalli, and David G. Gilbert. "Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers." Nicotine & Tobacco Research 23, no. 10 (April 12, 2021): 1779–86. http://dx.doi.org/10.1093/ntr/ntab072.
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Abstract Introduction Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine’s reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine. Methods Light smokers (n = 116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence ‘risk’ allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured. Results Across the sample, reward responsiveness was greater following nicotine compared to placebo (p = 0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received placebo first (p = 0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p < 0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p = 0.010) and were associated with blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine. Conclusion These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine’s effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population. Implications Individuals carrying genetic risk factors associated with nicotine dependence(rs16969968 A-allele carriers) and those with higher levels of depressive personality traits, showmore pronounced increases in reward learning following acute nicotine exposure. These findingssuggest that genetic and personality factors may drive individual differences in smoking trajectoriesin young light smokers by altering the degree to which nicotine enhances reward processing. Clinical trial registration NCT02129387 (pre-registered hypothesis: www.clinicaltrials.gov)
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Fu, Yitong, Shannon G. Matta, James D. Valentine, and Burt M. Sharp. "Adrenocorticotropin Response and Nicotine-Induced Norepinephrine Secretion in the Rat Paraventricular Nucleus Are Mediated through Brainstem Receptors*." Endocrinology 138, no. 5 (May 1, 1997): 1935–43. http://dx.doi.org/10.1210/endo.138.5.5122.
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Abstract Nicotine is a potent stimulus for the secretion of ACTH, and norepinephrinergic neurons originating in the brainstem are involved. Prior reports using in vivo microdialysis in alert rats have shown that nicotine, administered ip or into the fourth ventricle, stimulated the release of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN), the site of neurons containing CRH. In the present studies, rats received an iv infusion of nicotine into the jugular vein on alternate days during their active (dark) phase; therefore, direct correlations between the levels of NE microdialyzed from the PVN and plasma ACTH could be made in each animal. Nicotine administered iv (0.045–0.135 mg/kg) elicited dose-dependent increases in both NE and ACTH (P < 0.01). A significant correlation was found between nicotine-stimulated NE release in the PVN and ACTH secretion (r = 0.91, P < 0.01). To address whether the site(s) of action of nicotine was on presynaptic receptors on NE terminals in the PVN or on receptors on neurons in brainstem regions accessible from the fourth ventricle, the nicotinic cholinergic antagonist, mecamylamine (0.1–4.8 μg), was microinjected directly into the PVN or into the fourth ventricle before nicotine infusion. Fourth-ventricular administration of mecamylamine (1.6 μg) or higher, before iv nicotine (0.09 mg/kg), completely blocked both NE release in the PVN (IC50 = 0.64 μg) and ACTH secretion (IC50 = 0.40 μg) (P < 0.01, compared with vehicle before nicotine), whereas it was ineffective when injected directly into the PVN. The results demonstrate that the nicotinic cholinergic receptors in the brainstem, rather than presynaptic receptors within the PVN itself, mediate nicotine-stimulated PVN NE release and ACTH secretion.
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Blaim, K., and R. Ciszewska. "Badania procesu demetylacji nikotyny w warunkach in vivo [Investigations of nicotine demethylation process in vivo]." Acta Agrobotanica 26, no. 2 (2015): 303–9. http://dx.doi.org/10.5586/aa.1973.028.
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Investigations were carried out on intact leaves of <i>Nicotiana alata</i> which contain practically not alkaloids. Whey these leaves are infiltrated with nicotine it undergoes some chemical changes rather quickly. After introducing the nicotine into the leaves the alkaloid composition was investigated in three day intervals after the infiltration was stopped. No oxynicotine was present in the investigated material. The formation of nornicotine was determined quantitatively in outer and internal layers of the leaf blade. On the basis of these results determination of order and rate of nicotine demethylation was attempted. The reaction was classifield as a first order monomolecular reaction. In this connection a presumed mechanism of nicotine demethylation in leaves of <i>Nicotiana alata</i> was discussed.
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Hajiasgharzadeh, Khalil, Mohammad Hossein Somi, Behzad Mansoori, Mohammad Amin Doustvandi, Fatemeh Vahidian, Mohsen Alizadeh, Ahad Mokhtarzadeh, Dariush Shanehbandi, and Behzad Baradaran. "Alpha7 Nicotinic Acetylcholine Receptor Mediates Nicotine-induced Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma HepG2 Cells." Advanced Pharmaceutical Bulletin 10, no. 1 (December 11, 2019): 65–71. http://dx.doi.org/10.15171/apb.2020.008.
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Purpose: The cytotoxic properties upon treatment with nicotine have been reported in several studies, but the underlying mechanisms remain not fully defined. The alpha7 nicotinic acetylcholine receptor (α7nAChR) is one of the important nicotinic receptors, which nicotine partly by binding to this receptor exerts its effects. The current study aimed to investigates the influences of nicotine on cellular proliferative and apoptotic activities and tried to determine the involvement of α7nAChR in these functions. Methods: Human hepatocellular carcinoma (HepG2) cell line was used to determine the individual or combined effects of treatments with nicotine (10 μM) and specific siRNA (100 nM) targeting α7nAChR expression. The MTT assay, DAPI staining assay, and flow cytometry assay were applied to measure the cell viability, apoptosis and cell cycle progression of the cells, respectively. In addition, the changes in the mRNA level of the genes were assessed by qRT-PCR. Results: Compared to control groups, the cells treated with nicotine exhibited significant dosedependent decreases in cell viability (log IC50 = -5.12±0.15). Furthermore, nicotine induced apoptosis and cell cycle arrest especially at G2/M Phase. The qRT-PCR revealed that nicotine increased the mRNA levels of α7nAChR as well as caspase-3 and suppressed the expression of cyclin B1. Treatment with α7-siRNA abolished these effects of nicotine. Conclusion: These experiments determined that upregulation of α7nAChR by nicotine inhibits HepG2 cells proliferation and induces their apoptosis. These effects blocked by treatment with α7-siRNA, which indicates the involvement of α7nAChR pathways in these processes.
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Santoro, Alessia, Carlo Tomino, Giulia Prinzi, Palma Lamonaca, Vittorio Cardaci, Massimo Fini, and Patrizia Russo. "Tobacco Smoking: Risk to Develop Addiction, Chronic Obstructive Pulmonary Disease, and Lung Cancer." Recent Patents on Anti-Cancer Drug Discovery 14, no. 1 (March 13, 2019): 39–52. http://dx.doi.org/10.2174/1574892814666190102122848.
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Background: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis. Objective: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer. Methods: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (http://www.ncbi.nlm.nih.gov), Scopus (http://www.scopus.com), EMBASE (http://www.elsevier.com/online-tools/embase), and ISI Web of Knowledge (http://apps.webofknowledge.com/). The following searching terms: “nicotine”, “nicotinic receptor”, and “addiction” or “COPD” or “lung cancer” were used. </P><P> Patents were retrieved in clinicaltrials.gov (https://clinicaltrials.gov/). All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases. </P><P> New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported. Results: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation. Conclusion: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.
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Salim, Chinnu, Enkhzul Batsaikhan, Ann Ke Kan, Hao Chen, and Changhoon Jee. "Nicotine Motivated Behavior in C. elegans." International Journal of Molecular Sciences 25, no. 3 (January 29, 2024): 1634. http://dx.doi.org/10.3390/ijms25031634.
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To maximize the advantages offered by Caenorhabditis elegans as a high-throughput (HTP) model for nicotine dependence studies, utilizing its well-defined neuroconnectome as a robust platform, and to unravel the genetic basis of nicotine-motivated behaviors, we established the nicotine conditioned cue preference (CCP) paradigm. Nicotine CCP enables the assessment of nicotine preference and seeking, revealing a parallel to fundamental aspects of nicotine-dependent behaviors observed in mammals. We demonstrated that nicotine-elicited cue preference in worms is mediated by nicotinic acetylcholine receptors and requires dopamine for CCP development. Subsequently, we pinpointed nAChR subunits associated with nicotine preference and validated human GWAS candidates linked to nicotine dependence involved in nAChRs. Functional validation involves assessing the loss-of-function strain of the CACNA2D3 ortholog and the knock-out (KO) strain of the CACNA2D2 ortholog, closely related to CACNA2D3 and sharing human smoking phenotypes. Our orthogonal approach substantiates the functional conservation of the α2δ subunit of the calcium channel in nicotine-motivated behavior. Nicotine CCP in C. elegans serves as a potent affirmation of the cross-species functional relevance of GWAS candidate genes involved in nicotine seeking associated with tobacco abuse, providing a streamlined yet comprehensive system for investigating intricate behavioral paradigms within a simplified and reliable framework.