Journal articles on the topic 'Neuropeptides – Mechanism of action'
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Lestanova, Z., Z. Bacova, and Jan Bakos. "Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview." Endocrine Regulations 50, no. 2 (April 1, 2016): 72–82. http://dx.doi.org/10.1515/enr-2016-0011.
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AbstractThe present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the differences in the local responses elicited by neuropeptides, there exist certain functional similarities in the effects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42), implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.
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Chandrasekharan, Bindu, Behtash Ghazi Nezami, and Shanthi Srinivasan. "Emerging neuropeptide targets in inflammation: NPY and VIP." American Journal of Physiology-Gastrointestinal and Liver Physiology 304, no. 11 (June 1, 2013): G949—G957. http://dx.doi.org/10.1152/ajpgi.00493.2012.
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The enteric nervous system (ENS), referred to as the “second brain,” comprises a vast number of neurons that form an elegant network throughout the gastrointestinal tract. Neuropeptides produced by the ENS play a crucial role in the regulation of inflammatory processes via cross talk with the enteric immune system. In addition, neuropeptides have paracrine effects on epithelial secretion, thus regulating epithelial barrier functions and thereby susceptibility to inflammation. Ultimately the inflammatory response damages the enteric neurons themselves, resulting in deregulations in circuitry and gut motility. In this review, we have emphasized the concept of neurogenic inflammation and the interaction between the enteric immune system and enteric nervous system, focusing on neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). The alterations in the expression of NPY and VIP in inflammation and their significant roles in immunomodulation are discussed. We highlight the mechanism of action of these neuropeptides on immune cells, focusing on the key receptors as well as the intracellular signaling pathways that are activated to regulate the release of cytokines. In addition, we also examine the direct and indirect mechanisms of neuropeptide regulation of epithelial tight junctions and permeability, which are a crucial determinant of susceptibility to inflammation. Finally, we also discuss the potential of emerging neuropeptide-based therapies that utilize peptide agonists, antagonists, siRNA, oligonucleotides, and lentiviral vectors.
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Gołyszny, Miłosz, and Ewa Obuchowicz. "Are neuropeptides relevant for the mechanism of action of SSRIs?" Neuropeptides 75 (June 2019): 1–17. http://dx.doi.org/10.1016/j.npep.2019.02.002.
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Borg, Christian B., Nina Braun, Stephanie A. Heusser, Yasmin Bay, Daniel Weis, Iacopo Galleano, Camilla Lund, et al. "Mechanism and site of action of big dynorphin on ASIC1a." Proceedings of the National Academy of Sciences 117, no. 13 (March 12, 2020): 7447–54. http://dx.doi.org/10.1073/pnas.1919323117.
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Acid-sensing ion channels (ASICs) are proton-gated cation channels that contribute to neurotransmission, as well as initiation of pain and neuronal death following ischemic stroke. As such, there is a great interest in understanding the in vivo regulation of ASICs, especially by endogenous neuropeptides that potently modulate ASICs. The most potent endogenous ASIC modulator known to date is the opioid neuropeptide big dynorphin (BigDyn). BigDyn is up-regulated in chronic pain and increases ASIC-mediated neuronal death during acidosis. Understanding the mechanism and site of action of BigDyn on ASICs could thus enable the rational design of compounds potentially useful in the treatment of pain and ischemic stroke. To this end, we employ a combination of electrophysiology, voltage-clamp fluorometry, synthetic BigDyn analogs, and noncanonical amino acid-mediated photocrosslinking. We demonstrate that BigDyn binding results in an ASIC1a closed resting conformation that is distinct from open and desensitized states induced by protons. Using alanine-substituted BigDyn analogs, we find that the BigDyn modulation of ASIC1a is primarily mediated through electrostatic interactions of basic amino acids in the BigDyn N terminus. Furthermore, neutralizing acidic amino acids in the ASIC1a extracellular domain reduces BigDyn effects, suggesting a binding site at the acidic pocket. This is confirmed by photocrosslinking using the noncanonical amino acid azidophenylalanine. Overall, our data define the mechanism of how BigDyn modulates ASIC1a, identify the acidic pocket as the binding site for BigDyn, and thus highlight this cavity as an important site for the development of ASIC-targeting therapeutics.
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Bakkali-Kassemi, Lamiae, Seloua El Ouezzani, Rabia Magoul, Ikram Merroun, Maria Lopez-Jurado, and Mohammed Errami. "Effects of cannabinoids on neuropeptide Y and β-endorphin expression in the rat hypothalamic arcuate nucleus." British Journal of Nutrition 105, no. 4 (December 7, 2010): 654–60. http://dx.doi.org/10.1017/s0007114510004095.
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The control of appetite and satiety is extremely complex and involves a balance between neurotransmitters and neuropeptides to stimulate and/or inhibit feeding behaviour. The effect of cannabinoids on food intake is well established, but little is known about the mechanism of action underlying their activity. In the present report, the effect of pharmacological manipulation of the cannabinoid receptor on the expression of hypothalamic neuropeptides is investigated. We used an immunohistochemical approach to examine the effect of intracerebroventricular administration of the cannabinoid receptor agonist WIN55,212-2 and the inverse agonist AM251 on neuropeptide Y (NPY) and the β-endorphin (β-end) neuronal hypothalamic systems. Double immunohistochemistry (c-fos/β-end) was used to assess the number of β-end neurons activated by the cannabinoid agonist. The present results showed that 1 μg WIN 55,212-2 increases β-end immunoreactivity within the arcuate nucleus while no significant changes were noted in the NPY-immunoreactive nerve fibres network in comparison to the control group. Injection of 1 μg AM251 decreases both NPY and β-end immunoreactivity within the arcuate nucleus. The number of β-end neurons exhibiting c-fos increased significantly in WIN 55,212-2 compared with the control group. These results suggest that cannabinoids affect the expression of hypothalamic neuropeptides, notably the NPY and β-end systems, which may have implications in the orexigenic action of cannabinoids.
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Bodea, Alina, and Amorin Remus Popa. "Orectic And Anorectic Peptides And Their Implication In Obesity And The Metabolic Syndrome." Romanian Journal of Diabetes Nutrition and Metabolic Diseases 22, no. 2 (June 1, 2015): 187–91. http://dx.doi.org/10.1515/rjdnmd-2015-0023.
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AbstractBackground and aims: Cardiovascular diseases, diabetes mellitus, the metabolic syndrome and obesity are now globally widespread clinical conditions, addressing different ages, lately extending to young and children. The causes are multiple, involving an interaction between individual genetic risk factors and environmental factors. Many studies showed the importance of the hypothalamic neuropeptides and other neuropeptides in the regulation of the balance between food intake and energy consumption. We reviewed 25 recent research studies describing the physiological and physiopathological mechanisms of the orectic and anorectic peptides and their interaction to adjust the balance between food intake and energy expenditure.Conclusions: The hypothalamus, through its nuclei (arcuate and paraventricular) controls the balance between food intake and energy expenditure. The proopiomelanocortin (POMC) / Cocaine and amphetamine-related transcript (CART) neurons represent the anorectic centre. The neurons that release neuropeptide Y (NPY) and agouti-related protein (AgRP) by stimulation form the orectic centre. The neuropeptide Y (NPY) is the main hypothalamic orectic neuropeptide. Its action, besides stimulating the orectic effect, is to modulate the release of other hypothalamic orectic and anorectic neuropeptides. In addition, the energy balance is regulated by adipokines released by the adipose cells, hormones and neurotransmitters, blood glucose level and other metabolites.
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Petrera, Agnese, Beat Amstutz, Magda Gioia, Janine Hähnlein, Antonio Baici, Petra Selchow, Davide M. Ferraris, et al. "Functional characterization of the Mycobacterium tuberculosis zinc metallopeptidase Zmp1 and identification of potential substrates." Biological Chemistry 393, no. 7 (July 1, 2012): 631–40. http://dx.doi.org/10.1515/hsz-2012-0106.
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Abstract Zinc metallopeptidases of bacterial pathogens are widely distributed virulence factors and represent promising pharmacological targets. In this work, we have characterized Zmp1, a zinc metallopeptidase identified as a virulence factor of Mycobacterium tuberculosis and belonging to the neprilysin (NEP; M13) family, whose X-ray structure has been recently solved. Interestingly, this enzyme shows an optimum activity toward a fluorogenic substrate at moderately acidic pH values (i.e., 6.3), which corresponds to those reported for the Mtb phagosome where this enzyme should exert its pathological activity. Substrate specificity of Zmp1 was investigated by screening a peptide library. Several sequences derived from biologically relevant proteins were identified as possible substrates, including the neuropeptides bradykinin, neurotensin, and neuropeptide FF. Further, subsequences of other small bioactive peptides were found among most frequently cleaved sites, e.g., apelin-13 and substance P. We determined the specific cleavage site within neuropeptides by mass spectrometry, observing that hydrophobic amino acids, mainly phenylalanine and isoleucine, are overrepresented at position P1′. In addition, the enzymatic mechanism of Zmp1 toward these neuropeptides has been characterized, displaying some differences with respect to the synthetic fluorogenic substrate and indicating that the enzyme adapts its enzymatic action to different substrates.
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Werner, Felix-Martin, and Rafael Coveñas. "Neural Networks in Generalized Epilepsy and Novel Antiepileptic Drugs." Current Pharmaceutical Design 25, no. 4 (June 3, 2019): 396–400. http://dx.doi.org/10.2174/1381612825666190319121505.
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Background:In previous works, alterations of neurotransmitters and neuropeptides in the brain areas involved in generalized epilepsy have been reported.Objective:We reviewed the alterations of these neurotransmitters and neuropeptides in the following brain areas involved in generalized epilepsy: hippocampus, hypothalamus, thalamus and cerebral cortex. In these brain areas, the neural networks are also actualized. The mechanisms of action of newer antiepileptic drugs in the treatment of generalized epilepsy are also discussed.Results:Up-dating the neurotransmitter and neuropeptide alterations, we found that hippocampal GABAergic neurons presynaptically inhibit epileptogenic neurons via GABAB receptors. Epilepsy modulating neuropeptides (galanin, neuropeptide Y, dynorphin) are also involved. GABA deficiency, serotonin hyperactivity, dopamine hyperactivity and glutamate excitotoxicity can enhance ictogenesis: neurons containing these neurotransmitters form the main neural circuit. An increased excitability occurs when the alteration of these neurotransmitters is permanent.Conclusion:In preclinical studies, the GABAB receptor agonist GS 39,783 exerted a good antiepileptic effect. Perampanel, an AMPA receptor antagonist, showed good clinical effects in the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. In this treatment, perampanel can be combined with other antiepileptic drugs. Brivaracetam, which shows a high affinity for the synaptic vesicle 2A, exerted a good efficacy in the treatment of adult focal seizures and secondarily generalized tonic-clonic seizures.
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Dalvi, Prasad S., Anaies Nazarians-Armavil, Matthew J. Purser, and Denise D. Belsham. "Glucagon-Like Peptide-1 Receptor Agonist, Exendin-4, Regulates Feeding-Associated Neuropeptides in Hypothalamic Neurons in Vivo and in Vitro." Endocrinology 153, no. 5 (February 14, 2012): 2208–22. http://dx.doi.org/10.1210/en.2011-1795.
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Exendin-4, a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist, is a potential regulator of feeding behavior through its ability to inhibit gastric emptying, reduce food intake, and induce satiety. GLP-1R activation by exendin-4 induces anorexia; however, the specific populations of neuropeptidergic neurons activated by exendin-4 within the hypothalamus, the central regulator of energy homeostasis, remain unclear. This study determines whether exendin-4 regulates hypothalamic neuropeptide expression and explores the signaling mechanisms involved. The distribution and quantity of exendin-4-induced c-Fos immunoreactivity were evaluated to determine activation of α-melanocyte-stimulating hormone/proopiomelanocortin, neuropeptide Y, neurotensin (NT), and ghrelin neurons in hypothalamic nuclei during exendin-4-induced anorexia in mice. Additionally, exendin-4 action on NT and ghrelin transcript regulation was examined in immortalized hypothalamic neurons. With anorexia induced by intracerebroventricular exendin-4, α-melanocyte-stimulating hormone/proopiomelanocortin and neuropeptide Y neurons were activated in the arcuate nucleus, with simultaneous activation of NT-expressing neurons in the paraventricular nucleus, and ghrelin-expressing neurons in the arcuate nucleus, paraventricular nucleus, and periventricular hypothalamus, suggesting that neurons in one or more of these areas mediate the anorexic action of exendin-4. In the hypothalamic neuronal cell models, exendin-4 increased cAMP, cAMP response element-binding protein/activating transcription factor-1 and c-Fos activation, and via a protein kinase A-dependent mechanism regulated NT and ghrelin mRNA expression, indicating that these neuropeptides may serve as downstream mediators of exendin-4 action. These findings provide a previously unrecognized link between central GLP-1R activation by exendin-4 and the regulation of hypothalamic NT and ghrelin. Further understanding of this central GLP-1R activation may lead to safe and effective therapeutics for the treatment of metabolic disorders.
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Zingale, Gabriele Antonio, Francesco Bellia, Ikhlas Mohamed Mohamud Ahmed, Przemyslaw Mielczarek, Jerzy Silberring, and Giuseppe Grasso. "IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism." International Journal of Molecular Sciences 20, no. 18 (September 10, 2019): 4447. http://dx.doi.org/10.3390/ijms20184447.
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Insulin-degrading enzyme (IDE) was applied to catalyze hydrolysis of Nociceptin/Orphanin 1-16 (OFQ/N) to show the involvement of the enzyme in degradation of neuropeptides engaged in pain transmission. Moreover, IDE degradative action towards insulin (Ins) was inhibited by the OFQ/N fragments, suggesting a possible regulatory mechanism in the central nervous system. It has been found that OFQ/N and Ins affect each other degradation by IDE, although in a different manner. Indeed, while the digestion of OFQ/N is significantly affected by the presence of Ins, the kinetic profile of the Ins hydrolysis is not affected by the presence of OFQ/N. However, the main hydrolytic fragments of OFQ/N produced by IDE exert inhibitory activity towards the IDE-mediated Ins degradation. Here, we present the results indicating that, besides Ins, IDE cleaves neuropeptides and their released fragments act as inhibitors of IDE activity toward Ins. Having in mind that IDE is present in the brain, which also contains Ins receptors, it cannot be excluded that this enzyme indirectly participates in neural communication of pain signals and that neuropeptides involved in pain transmission may contribute to the regulation of IDE activity. Finally, preliminary results on the metabolism of OFQ/N, carried out in the rat spinal cord homogenate in the presence of various inhibitors specific for different classes of proteases, show that OFQ/N proteolysis in rat spinal cord could be due, besides IDE, also to a cysteine protease not yet identified.
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Kumamoto, Eiichi. "Cellular Mechanisms for Antinociception Produced by Oxytocin and Orexins in the Rat Spinal Lamina II—Comparison with Those of Other Endogenous Pain Modulators." Pharmaceuticals 12, no. 3 (September 16, 2019): 136. http://dx.doi.org/10.3390/ph12030136.
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Much evidence indicates that hypothalamus-derived neuropeptides, oxytocin, orexins A and B, inhibit nociceptive transmission in the rat spinal dorsal horn. In order to unveil cellular mechanisms for this antinociception, the effects of the neuropeptides on synaptic transmission were examined in spinal lamina II neurons that play a crucial role in antinociception produced by various analgesics by using the whole-cell patch-clamp technique and adult rat spinal cord slices. Oxytocin had no effect on glutamatergic excitatory transmission while producing a membrane depolarization, γ-aminobutyric acid (GABA)-ergic and glycinergic spontaneous inhibitory transmission enhancement. On the other hand, orexins A and B produced a membrane depolarization and/or a presynaptic spontaneous excitatory transmission enhancement. Like oxytocin, orexin A enhanced both GABAergic and glycinergic transmission, whereas orexin B facilitated glycinergic but not GABAergic transmission. These inhibitory transmission enhancements were due to action potential production. Oxytocin, orexins A and B activities were mediated by oxytocin, orexin-1 and orexin-2 receptors, respectively. This review article will mention cellular mechanisms for antinociception produced by oxytocin, orexins A and B, and discuss similarity and difference in antinociceptive mechanisms among the hypothalamic neuropeptides and other endogenous pain modulators (opioids, nociceptin, adenosine, adenosine 5’-triphosphate (ATP), noradrenaline, serotonin, dopamine, somatostatin, cannabinoids, galanin, substance P, bradykinin, neuropeptide Y and acetylcholine) exhibiting a change in membrane potential, excitatory or inhibitory transmission in the spinal lamina II neurons.
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Bliźniewska-Kowalska, Katarzyna, Maria Łukasik, and Piotr Gałecki. "Cerebrolysin – mechanism of action and application in psychiatry and neurology." Pharmacotherapy in Psychiatry and Neurology 35, no. 1 (March 29, 2019): 9–23. http://dx.doi.org/10.33450/fpn.2019.03.002.
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Cerebrolysin is a medication, which has been used in psychiatry and neurology for over 50 years. The aim of this paper is to present the current state of knowledge on cerebrolysin. It is a non-lipid mixture of free L-amino acids and neuropeptides of low molecular weight that are purified via enzymatic proteolysis from brains of young pigs. It also contains magnesium, phosphorus, potassium and selenium. Cerebrolysin passes the blood-brain barrier. It was proved that it supports endogenous regeneration processes, mimics the behaviour of neurotrophic factors and modifies their level, affects the Sonic Hedgehog protein’s signalling pathway, protects from the pathological events and cascades which stem from an injury or a neurodegenerative disease, reduces amounts of free radicals as well as pro-apoptotic enzymes, modulates inflammatory response and also affects neuroplasticity and neurogenesis. Because of these characteristics, cerebrolysin is used in treatment of patients suffering from strokes, traumatic brain injuries, patients with cognitive disorders, including Alzheimer’s dementia and vascular dementia. The standard route of administration is via injections; however, some research was conducted on oral administration as well. The commonly reported adverse effects of cerebrolysin are transient and of mild severity. Results of research on the effectiveness and safety of cerebrolysin seem to be encouraging. They confirm high safety level and theoretical legitimacy of its use. The treatment of patients with organic, metabolic and neurodegenerative syndromes is difficult and often ineffective. Therefore, every available method of treatment needs to be taken under consideration.
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Lagrange, Andre H. "Valproate Enhances Neuropeptide Y Expression: Modulating the Modulators." Epilepsy Currents 7, no. 4 (July 2007): 107–9. http://dx.doi.org/10.1111/j.1535-7511.2007.00167.x.
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Chronic Valproic Acid Treatment Triggers Increased Neuropeptide Y Expression and Signaling in Rat Nucleus Reticularis Thalami. Brill J, Lee M, Zhao S, Fernald RD, Huguenard JR. J Neurosci 2006;26:6813–6822. Valproate (VPA) can suppress absence and other seizures, but its precise mechanisms of action are not completely understood. We investigated whether VPA influences the expression of neuropeptide Y (NPY), an endogenous anticonvulsant. Chronic VPA administration to young rats (300–600 mg · kg–1 · d–1 in divided doses over 4 d) resulted in a 30–50% increase in NPY mRNA and protein expression in the nucleus reticularis thalami (nRt) and hippocampus, but not in the neocortex, as shown by real-time PCR, radioimmunoassay, and immunohistochemistry. No increased expression was observed after a single acute dose of VPA. Chronic treatment with the pharmacologically inactive VPA analog octanoic acid did not elicit changes in NPY expression. No significant expression changes could be shown for the mRNAs of the Y1 receptor or of the neuropeptides somatostatin, vasoactive intestinal polypeptide, and choleocystokinin. Fewer synchronous spontaneous epileptiform oscillations were recorded in thalamic slices from VPA-treated animals, and oscillation duration as well as the period of spontaneous and evoked oscillations were decreased. Application of the Y1 receptor inhibitor N2-(diphenylacetyl)- N-[(4-hydroxyphenyl)methyl]-d-arginine-amide (BIBP3226) enhanced thalamic oscillations, indicating that NPY is released during those oscillations and acts to downregulate oscillatory strength. Chronic VPA treatment significantly potentiated the effect of BIBP3226 on oscillation duration but not on oscillation period. These results demonstrate a novel mechanism for the antiepileptic actions of chronic VPA therapy.
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Hansen, Jakob Møller, Jan Fahrenkrug, Jesper Petersen, Troels Wienecke, Karsten Skovgaard Olsen, and Messoud Ashina. "Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the circulation after sumatriptan." Scandinavian Journal of Pain 4, no. 4 (October 1, 2013): 211–16. http://dx.doi.org/10.1016/j.sjpain.2013.04.002.
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AbstractBackground and purposeThe origin of migraine pain is still elusive, but increasingly researchers focus on the neuropeptides in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. The parasympathetic neurotransmitters, pituitary adenylate cyclase activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) may be released from parasympathetic fibres and activate sensory nerve fibres during migraine attacks. Triptans are effective and well tolerated in acute migraine management but the exact mechanism of action is still debated. Triptans might reduce circulating neuropeptides. To examine this question, we examined the effect of sumatriptan on VIP and PACAP levels in vivo, under conditions without trigeminovascular system activation.MethodsIn 16 healthy volunteers we measured VIP and PACAP levels before and after administration of subcutaneous sumatriptan. We simultaneously collected blood samples from the internal and external jugular, the cubital veins and the radial artery, thereby covering both the cerebral and systemic circulation. VIP and PACAP determinations were assayed blindly with respect to timing and vascular compartments, but with all samples of a patient in the same assay, to minimize the influence of interassay variation.ResultsWe found no difference in VIP and PACAP concentrations between the internal and external jugular, the cubital veins and the radial artery, (P>0.05), and the circulating levels of VIP and PACAP did not change over time (P>0.05). We found excellent agreement between neuropeptide levels in the internal and the external jugular system.ConclusionSumatriptan did not change the levels of circulating VIP and PACAP in the intra or extra cerebral circulation in healthy volunteers. Under baseline conditions, without trigeminovascular activation, sumatriptan does not affect the release of neuropeptides VIP and PACAP.ImplicationsOur results indicate no effect of 5-HT1B/D receptor activation on circulating levels of VIP and PACAP in humans without trigeminovascular activation. Given that neuropeptides play an important role for migraine it would be interesting to conduct a similar study in a migraine population.
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Zandawala, Meet, Thomas Nguyen, Marta Balanyà Segura, Helena A. D. Johard, Mirjam Amcoff, Christian Wegener, Jean-Paul Paluzzi, and Dick R. Nässel. "A neuroendocrine pathway modulating osmotic stress in Drosophila." PLOS Genetics 17, no. 3 (March 8, 2021): e1009425. http://dx.doi.org/10.1371/journal.pgen.1009425.
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Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. In recent years, much progress has been made on the mechanisms and neuropeptides that regulate responses to metabolic/nutritional stress, as well as those involved in countering osmotic and ionic stresses. Here, we identified a peptidergic pathway that links these types of regulatory functions. We uncover the neuropeptide Corazonin (Crz), previously implicated in responses to metabolic stress, as a neuroendocrine factor that inhibits the release of a diuretic hormone, CAPA, and thereby modulates the tolerance to osmotic and ionic stress. Both knockdown ofCrzand acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Mapping of the Crz receptor (CrzR) expression identified three pairs ofCapa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We show that Crz acts to restore water/ion homeostasis by inhibiting release of CAPA neuropeptides via inhibition of cAMP production in Va neurons. Knockdown ofCrzRin Va neurons affects CAPA signaling, and consequently increases tolerance for desiccation, ionic stress and starvation, but delays chill-coma recovery. Optogenetic activation of Va neurons stimulates excretion and simultaneous activation of Crz and CAPA-expressing neurons reduces this response, supporting the inhibitory action of Crz. Thus, Crz inhibits Va neurons to maintain osmotic and ionic homeostasis, which in turn affects stress tolerance. Earlier work demonstrated that systemic Crz signaling restores nutrient levels by promoting food search and feeding. Here we additionally propose that Crz signaling also ensures osmotic homeostasis by inhibiting release of CAPA neuropeptides and suppressing diuresis. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body inDrosophila.
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Koh, H. Y., F. S. Vilim, J. Jing, and K. R. Weiss. "Two Neuropeptides Colocalized in a Command-Like Neuron Use Distinct Mechanisms to Enhance Its Fast Synaptic Connection." Journal of Neurophysiology 90, no. 3 (September 2003): 2074–79. http://dx.doi.org/10.1152/jn.00358.2003.
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In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia, we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size ( q) and CP2 increases the calculated quantal content ( m) of EPSPs. Since the PSP amplitude represents the product of q and m, the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron.
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Augustyniak, Daria, Eliza Kramarska, Paweł Mackiewicz, Magdalena Orczyk-Pawiłowicz, and Fionnuala T. Lundy. "Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis." International Journal of Molecular Sciences 22, no. 7 (April 1, 2021): 3658. http://dx.doi.org/10.3390/ijms22073658.
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The regulation of infection and inflammation by a variety of host peptides may represent an evolutionary failsafe in terms of functional degeneracy and it emphasizes the significance of host defense in survival. Neuropeptides have been demonstrated to have similar antimicrobial activities to conventional antimicrobial peptides with broad-spectrum action against a variety of microorganisms. Neuropeptides display indirect anti-infective capacity via enhancement of the host’s innate and adaptive immune defense mechanisms. However, more recently concerns have been raised that some neuropeptides may have the potential to augment microbial virulence. In this review we discuss the dual role of neuropeptides, perceived as a double-edged sword, with antimicrobial activity against bacteria, fungi, and protozoa but also capable of enhancing virulence and pathogenicity. We review the different ways by which neuropeptides modulate crucial stages of microbial pathogenesis such as adhesion, biofilm formation, invasion, intracellular lifestyle, dissemination, etc., including their anti-infective properties but also detrimental effects. Finally, we provide an overview of the efficacy and therapeutic potential of neuropeptides in murine models of infectious diseases and outline the intrinsic host factors as well as factors related to pathogen adaptation that may influence efficacy.
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Morara, Stefano, Anna Maria Colangelo, and Luciano Provini. "Microglia-Induced Maladaptive Plasticity Can Be Modulated by NeuropeptidesIn Vivo." Neural Plasticity 2015 (2015): 1–15. http://dx.doi.org/10.1155/2015/135342.
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Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activityin vitro. More relevantly, this regulator activity has been assessed alsoin vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticityin vivoand how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies.
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Leonard, B. E. "Neuropsychopharmacology: Changing the Face of Psychotropic Drug Discovery." CNS Spectrums 2, no. 9 (October 1997): 26–34. http://dx.doi.org/10.1017/s1092852900005162.
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AbstractThis review speculates on the changes currently taking place in psychopharmacology that will alter the course of psychotropic drug discovery and application in the coming millennium. The importance of endocoids as causative agents in central nervous system diseases; the role of neuropeptides and “trace” amine transmitters; the impact of imaging methods in elucidating the mechanism of action of psychotropic drugs; gene therapy; and the new role of psychoneuroimmunology in drug discovery are predicted to have a major impact in both the research and development of new psychotropic drugs in the twenty-first century.
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Norman, Trevor R. "Prospects for the Treatment of Depression." Australian & New Zealand Journal of Psychiatry 40, no. 5 (May 2006): 394–401. http://dx.doi.org/10.1080/j.1440-1614.2006.01814.x.
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Antidepressant drugs represent the principal form of treatment for major depressive disorder. While there are a plethora of medications available for this task, current drugs have many shortcomings. In the face of these deficiencies there is an ongoing search for new agents. The search has been guided, in part, by drug design based on existing agents and their putative mechanism of action. This has been less than fruitful in addressing inadequacies of existing medications as it has not produced compounds which are novel in terms of pharmacological mechanisms. Recent insights from molecular biological approaches hold promise for the discovery of novel compounds, in particular the so-called neurogenesis hypothesis suggests novel therapeutic approaches. Although significantly modified over the years, the monoamine hypothesis of depression and antidepressant drug action still remains an important driving force behind the development of new compounds. Several recently marketed agents and some in early-phase development tend to conform to these existing mechanistic hypotheses. Clearly the place of these agents in the treatment of depression is dependent on issues such as short- and long-term safety and efficacy. Duloxetine has been developed as a dual monoamine re-uptake inhibitor. Agomelatine is a compound with major effects on the circadian system as well as effects on subtypes of the serotonin receptor system. While the mechanism of action of this compound is not certain, recent evidence would suggest that the drug exerts its effects through antagonist actions at serotonin receptors. Compounds based on the hypothalamic pituitary adrenal axis, substance P antagonism and other neuropeptides have potential application for the treatment of depression but require further development before that potential is realized.
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Teaney, Nicole A., and Nicole E. Cyr. "Sirtuin 1 Regulates Synapsin 1 in POMC-Producing N43-5 Neurons via FOXO1." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A56—A57. http://dx.doi.org/10.1210/jendso/bvab048.114.
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Abstract The nutrient-sensor protein Sirtuin 1 (Sirt1; silent mating type information regulation 2 homolog 1) has been shown to have significant and opposing effects on insulin resistance, leptin resistance, and body weight in the periphery and the brain. In the hypothalamic arcuate nucleus (ARC) of the brain, Sirt1 increases in the obese state and acts to promote weight gain as well as insulin and leptin resistance by increasing the orexigenic neuropeptides Agouti-related protein (AgRP) and neuropeptide Y (NPY), and in a distinct set of ARC neurons, by decreasing POMC and thus its anorexigenic derivative alpha-melanocyte stimulating hormone (alpha-MSH) (1). Sirt1’s actions on these neuropeptides are mediated at least in part by the deacetylation of the transcription factor forkhead box O1 (FOXO1). Another mechanism by which Sirt1 regulates body weight appears to be through mediating changes in the synapses of these neuropeptide-producing ARC neurons. For example, a previous study demonstrated that Sirt1 inhibition with the specific Sirt1 inhibitor, Ex-527, decreased AgRP-NPY inhibitory synaptic input on POMC neurons, which suggests that the obesity-induced increase in ARC Sirt1 would increase AgRP-NPY inhibition of POMC neurons thus promoting weight gain (2). The present study investigated how Sirt1 regulates synapses specifically in POMC-producing N43-5 neurons. Results reveal that inhibition of Sirt1 with Ex-527 significantly increased the presynaptic marker Synapsin 1 (Syn1) in N43-5 neurons. Furthermore, we investigated whether the Sirt1 target, FOXO1, mediates these synaptic changes. FOXO1 overexpression significantly decreased Syn1 and transfection of mutant FOXO1 significantly increased Syn1. Overall, our results suggest that Sirt1 regulates synapses of POMC neurons and does so in a manner that differs from Sirt1’s regulation of AgRP-NPY neuronal synapses. Future work will elucidate the mechanisms and consequences of Sirt1 and FOXO1 regulation of POMC neuron synapses under different nutritional conditions in vitro and in vivo. (1) Cyr, N. E., Steger, J. S., Toorie, A. M., Yang, J. Z., Stuart, R., Nillni, E. A. (2014). Central Sirt1 Regulates Body Weight and Energy Expenditure Along With the POMC-Derived Peptide α-MSH and the Processing Enzyme CPE Production in Diet-Induced Obese Male Rats, Endocrinology, 155(7), 2423–2435. (2) Dietrich, M. O., Antunes, C., Geliang, G., Liu, Z., Borok, E., Nie, Y., . . . Horvath, T. L. (2010). Agrp neurons mediate Sirt1’s action on the melanocortin system and energy balance: Roles for Sirt1 in neuronal firing and synaptic plasticity. The Journal of Neuroscience, 30(35), 11815–11825.
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Sánchez, Edith, Praful S. Singru, Runa Acharya, Monica Bodria, Csaba Fekete, Ann Marie Zavacki, Antonio C. Bianco, and Ronald M. Lechan. "Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus." Endocrinology 149, no. 9 (May 8, 2008): 4329–35. http://dx.doi.org/10.1210/en.2008-0411.
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To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 ± 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.
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Simon, Ádám, András Jávor, and Levente Czeglédi. "Role of hypothalamic neuropeptides in feed intake regulation of livestock species (literary review)." Acta Agraria Debreceniensis, no. 65 (March 24, 2015): 63–68. http://dx.doi.org/10.34101/actaagrar/65/1879.
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Energy balance is the net result of the energy intake (nutrition) and expenditure (basic metabolic rate). The purpose of the daily feed intake is to provide energy and nutrients for maintenance, production and fill and maintain energy storages in form of glycogen and fat. Animals can adjust their feed intake to ensure their energy demand. Food intake regulation in animals and human is a very complex process, in which the digestive system, the central nervous system, the joining hormonal and non-hormonal factors, and the integrating hypothalamus take part. This review primarily focuses on the action mechanism of some important appetite regulating neuropeptides, and their impacts on the performance traits of the economically significant animal species.
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Jarry, Marie, Mickaël Diallo, Céline Lecointre, Laurence Desrues, Tursonjan Tokay, David Chatenet, Jérôme Leprince, et al. "The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: involvement in cell proliferation." Biochemical Journal 428, no. 1 (April 28, 2010): 113–24. http://dx.doi.org/10.1042/bj20090867.
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UII (urotensin II) and its paralogue URP (UII-related peptide) are two vasoactive neuropeptides whose respective central actions are currently unknown. In the present study, we have compared the mechanism of action of URP and UII on cultured astrocytes. Competition experiments performed with [125I]UII showed the presence of very-high- and high-affinity binding sites for UII, and a single high-affinity site for URP. Both UII and URP provoked a membrane depolarization accompanied by a decrease in input resistance, stimulated the release of endozepines, neuropeptides specifically produced by astroglial cells, and generated an increase in [Ca2+]c (cytosolic Ca2+ concentration). The UII/URP-induced [Ca2+]c elevation was PTX (pertussis toxin)-insensitive, and was blocked by the PLC (phospholipase C) inhibitor U73122 or the InsP3 channel blocker 2-APB (2-aminoethoxydiphenylborane). The addition of the Ca2+ chelator EGTA reduced the peak and abolished the plateau phase, whereas the T-type Ca2+ channel blocker mibefradil totally inhibited the Ca2+ response evoked by both peptides. However, URP and UII induced a mono- and bi-phasic dose-dependent increase in [Ca2+]c and provoked short- and long-lasting Ca2+ mobilization respectively. Similar mono- and bi-phasic dose-dependent increases in [3H]inositol incorporation into polyphosphoinositides in astrocytes was obtained, but the effect of UII was significantly reduced by PTX, although BRET (bioluminescence resonance energy transfer) experiments revealed that both UII and URP recruited Gαo-protein. Finally, UII, but not URP, exerted a dose-dependent mitogenic activity on astrocytes. Therefore we described that URP and UII exert not only similar, but also divergent actions on astrocyte activity, with UII exhibiting a broader range of activities at physiological peptide concentrations.
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Larivière, Sigolène, Ghislaine Garrel-Lazayres, Violaine Simon, Norihito Shintani, Akemichi Baba, Raymond Counis, and Joëlle Cohen-Tannoudji. "Gonadotropin-Releasing Hormone Inhibits Pituitary Adenylyl Cyclase-Activating Polypeptide Coupling to 3′,5′-Cyclic Adenosine-5′-Monophosphate Pathway in LβT2 Gonadotrope Cells through Novel Protein Kinase C Isoforms and Phosphorylation of Pituitary Adenylyl Cyclase-Activating Polypeptide Type I Receptor." Endocrinology 149, no. 12 (August 28, 2008): 6389–98. http://dx.doi.org/10.1210/en.2008-0504.
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Gonadotrope cells are primarily regulated by GnRH but are also targets of the pituitary adenylyl cyclase-activating polypeptide (PACAP). Although it has been reported that reciprocal interactions between both neuropeptides contribute to regulation of gonadotrope function, the underlying mechanisms remain poorly understood. In this study, we reevaluated PACAP coupling to the cAMP pathway in LβT2 gonadotrope cells and analyzed GnRH effect on PACAP signaling. We established that PACAP38 markedly increases intracellular cAMP levels (EC50 of 4.7 ± 1.3 nm) through the PACAP type 1 receptor (PAC1-R), as evidenced by pharmacological and RT-PCR studies. Interestingly, although GnRH couples to cAMP pathway in LβT2 cells, the effects of both neuropeptides were not synergistic. Instead, the GnRH agonist (GnRHa) triptorelin rapidly and strongly inhibited (70% inhibition as early as 5 min) PACAP38-induced cAMP production. Inhibition was calcium independent, mimicked by the phorbol ester phorbol 12-myristate 13-acetate, and blocked by the protein kinase C (PKC) inhibitor bisindoylmaleimide, indicating that GnRHa inhibitory action relies on PKC. Selective down-regulation of both conventional and novel PKC prevented a GnRHa effect, whereas pharmacological inhibition of conventional PKC only was ineffective, strongly suggesting the involvement of novel PKC isoforms. GnRHa did not inhibit forskolin- or cholera toxin-stimulated cAMP accumulation, suggesting that PAC1-R is the predominant target of GnRH. Accordingly, we demonstrated for the first time that GnRH increases PAC1-R phosphorylation through PKC, providing a potential molecular mechanism which may account for GnRH inhibitory effect.
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Caricilli, Andrea M., Erica Penteado, Lélia L. de Abreu, Paula G. F. Quaresma, Andressa C. Santos, Dioze Guadagnini, Daniella Razolli, et al. "Topiramate Treatment Improves Hypothalamic Insulin and Leptin Signaling and Action and Reduces Obesity in Mice." Endocrinology 153, no. 9 (September 1, 2012): 4401–11. http://dx.doi.org/10.1210/en.2012-1272.
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Topiramate (TPM) treatment has been shown to reduce adiposity in humans and rodents. The reduction in adiposity is related to decreased food intake and increased energy expenditure. However, the molecular mechanisms through which TPM induces weight loss are contradictory and remain to be clarified. Whether TPM treatment alters hypothalamic insulin, or leptin signaling and action, is not well established. Thus, we investigate herein whether short-term TPM treatment alters energy balance by affecting insulin and leptin signaling, action, or neuropeptide expression in the hypothalamus of mice fed with a high-fat diet. As expected, short-term treatment with TPM diminished adiposity in obese mice mainly due to reduced food intake. TPM increased anorexigenic signaling by enhancing the leptin-induced leptin receptor/Janus kinase 2/signal transducer and activator of transcription 3 pathway and the insulin-induced insulin receptor substrate/Akt/forkhead box O1 pathway in parallel to reduced phosphatase protein expression in the hypothalamus of obese mice. These effects were independent of body weight. TPM also raised anorexigenic neuropeptides such as POMC, TRH, and CRH mRNA levels in obese mice. In addition, TPM increased the activation of the hypothalamic MAPK/ERK pathway induced by leptin, accompanied by an increase in peroxisome proliferator-activated receptor-coactivator α and uncoupling protein 1 protein levels in brown adipose tissue. Furthermore, TPM increased AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation in peripheral tissues, which may help improve energy metabolism in these tissues. Together, these results provide novel insights into the molecular mechanisms through which TPM treatment reduces adiposity.
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Gariano, R. F., and P. M. Groves. "A mechanism for the involvement of colocalized neuropeptides in the actions of antipsychotic drugs." Biological Psychiatry 26, no. 3 (July 1989): 303–14. http://dx.doi.org/10.1016/0006-3223(89)90043-7.
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Kasprzak, Aldona, and Agnieszka Adamek. "The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management." International Journal of Molecular Sciences 21, no. 10 (May 15, 2020): 3494. http://dx.doi.org/10.3390/ijms21103494.
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Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.
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Bradley, Richard L., Julia P. R. Mansfield, Eleftheria Maratos-Flier, and Bentley Cheatham. "Melanin-concentrating hormone activates signaling pathways in 3T3-L1 adipocytes." American Journal of Physiology-Endocrinology and Metabolism 283, no. 3 (September 1, 2002): E584—E592. http://dx.doi.org/10.1152/ajpendo.00161.2002.
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Energy homeostasis is regulated by peripheral signals, such as leptin, and by several orexigenic and anorectic neuropeptides. Recently, we reported that the orexigenic neuropeptide melanin-concentrating hormone (MCH) stimulates leptin production by rat adipocytes and that the MCH receptor (MCH-R1) is present on these cells. Here, we show that MCH-R1 is present on murine 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with 1 μM MCH for up to 2 h acutely downregulated MCH-R1, indicating a mechanism of ligand-induced receptor downregulation. Potential signaling pathways mediating MCH-R1 action in adipocytes were investigated. Treatment of 3T3-L1 adipocytes with 1 μM MCH rapidly induced a threefold and a fivefold increase in p44/42 MAPK and pp70 S6 kinase activities, respectively. In addition, 3T3-L1 adipocytes transiently transfected with a murine leptin-luciferase promoter construct showed a fourfold and a sixfold increase in leptin promoter-reporter gene expression at 1 h and 4 h, respectively, in response to MCH. Activity decreased to basal levels at 8 h. Furthermore, MCH-stimulated leptin promoter-driven luciferase activity was diminished in the presence of the MAP/ERK kinase inhibitor PD-98059 and in the presence of rapamycin, an inhibitor of pp70 S6 kinase activation. These results provide further evidence for a functional MCH signaling pathway in adipocytes.
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Ren, Wenjie, Takaki Kiritoshi, Stéphanie Grégoire, Guangchen Ji, Remo Guerrini, Girolamo Calo, and Volker Neugebauer. "Neuropeptide S: a novel regulator of pain-related amygdala plasticity and behaviors." Journal of Neurophysiology 110, no. 8 (October 15, 2013): 1765–81. http://dx.doi.org/10.1152/jn.00874.2012.
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Amygdala plasticity is an important contributor to the emotional-affective dimension of pain. Recently discovered neuropeptide S (NPS) has anxiolytic properties through actions in the amygdala. Behavioral data also suggest antinociceptive effects of centrally acting NPS, but site and mechanism of action remain to be determined. This is the first electrophysiological analysis of pain-related NPS effects in the brain. We combined whole cell patch-clamp recordings in brain slices and behavioral assays to test the hypothesis that NPS activates synaptic inhibition of amygdala output to suppress pain behavior in an arthritis pain model. Recordings of neurons in the laterocapsular division of the central nucleus (CeLC), which serves pain-related amygdala output functions, show that NPS inhibited the enhanced excitatory drive [monosynaptic excitatory postsynaptic currents (EPSCs)] from the basolateral amygdala (BLA) in the pain state. As shown by miniature EPSC analysis, the inhibitory effect of NPS did not involve direct postsynaptic action on CeLC neurons but rather a presynaptic, action potential-dependent network mechanism. Indeed, NPS increased external capsule (EC)-driven synaptic inhibition of CeLC neurons through PKA-dependent facilitatory postsynaptic action on a cluster of inhibitory intercalated (ITC) cells. NPS had no effect on BLA neurons. High-frequency stimulation (HFS) of excitatory EC inputs to ITC cells also inhibited synaptic activation of CeLC neurons, providing further evidence that ITC activation can control amygdala output. The cellular mechanisms by which EC-driven synaptic inhibition controls CeLC output remain to be determined. Administration of NPS into ITC, but not CeLC, also inhibited vocalizations and anxiety-like behavior in arthritic rats. A selective NPS receptor antagonist ([d-Cys(tBu)5]NPS) blocked electrophysiological and behavioral effects of NPS. Thus NPS is a novel tool to control amygdala output and pain-related affective behaviors through a direct action on inhibitory ITC cells.
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Brain, S. D., P. Newbold, and R. Kajekar. "Modulation of the release and activity of neuropeptides in the microcirculation." Canadian Journal of Physiology and Pharmacology 73, no. 7 (July 1, 1995): 995–98. http://dx.doi.org/10.1139/y95-139.
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Electrical stimulation of the sensory saphenous nerve leads to neurogenic edema formation in the innervated area of the paw of the anesthetized rat. Evidence suggests that the edema formation is the result of increased microvascular permeability mediated via neurokinin NK1 receptors and increased blood flow mediated via calcitonin gene related peptide CGRP1 receptors. Results indicate that selective receptor antagonists will only inhibit the response mediated by the specific receptor they antagonise. In the case of neurogenic inflammation, where it is common for more than one biologically active neuropeptide to be released concomitantly, it may be more sensible to develop agents that inhibit neuropeptide release. The effects of some agents suggested to affect neurogenic responses are presented. The anti-inflammatory steroid dexamethasone (1 mg/kg subcutaneously, −4 h) significantly (p < 0.01) inhibited edema formation, but the mechanism of action is likely to be related to the general anti-edema effect of dexamethasone. In contrast the anti-asthma agent nedocromil sodium (up to 10 mg/kg intravenously, −15 min) and the histamine H3 agonist (R)-α-methyl histamine (1–10 mg/kg intravenously, −5 min) both failed to inhibit saphenous nerve induced edema formation, despite positive results in other sensory nerve systems. The results are discussed in the context of evidence obtained using other agents in skin.Key words: neurogenic inflammation, substance P, calcitonin gene related peptide, edema.
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Chowdhury, Vishwajit S., Kazutoshi Yamamoto, Izumi Saeki, Itaru Hasunuma, Taichi Shimura, and Kazuyoshi Tsutsui. "Melatonin Stimulates the Release of Growth Hormone and Prolactin by a Possible Induction of the Expression of Frog Growth Hormone-Releasing Peptide and Its Related Peptide-2 in the Amphibian Hypothalamus." Endocrinology 149, no. 3 (December 6, 2007): 962–70. http://dx.doi.org/10.1210/en.2007-1427.
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We recently identified a novel hypothalamic neuropeptide stimulating GH release in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP-2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals containing these neuropeptides are localized in the suprachiasmatic nucleus (SCN) and median eminence, respectively. To understand the physiological role of fGRP and fGRP-RP-2, we investigated the mechanisms that regulate the expression of these neuropeptides. This study shows that melatonin induces the expression of fGRP and fGRP-RPs in bullfrogs. Orbital enucleation combined with pinealectomy (Ex plus Px) decreased the expression of fGRP precursor mRNA and content of mature fGRP and fGRP-RPs in the diencephalon including the SCN and median eminence. Conversely, melatonin administration to Ex plus Px bullfrogs increased dose-dependently their expressions. The expression of fGRP precursor mRNA was photoperiodically controlled and increased under short-day photoperiods, when the nocturnal duration of melatonin secretion increases. To clarify the mode of melatonin action on the induction of fGRP and fGRP-RPs, we further demonstrated the expression of Mel1b, a melatonin receptor subtype, in SCN neurons expressing fGRP precursor mRNA. Finally, we investigated circulating GH and PRL levels after melatonin manipulation because fGRP and fGRP-RP-2 stimulate the release of GH and GH/PRL, respectively. Ex plus Px decreased plasma GH and PRL concentrations, whereas melatonin administration increased these hormone levels. These results suggest that melatonin induces the expression of fGRP and fGRP-RP-2, thus stimulating the release of GH and PRL in bullfrogs.
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Donkin, James J., Alan J. Nimmo, Ibolja Cernak, Peter C. Blumbergs, and Robert Vink. "Substance P is Associated with the Development of Brain Edema and Functional Deficits after Traumatic Brain Injury." Journal of Cerebral Blood Flow & Metabolism 29, no. 8 (May 13, 2009): 1388–98. http://dx.doi.org/10.1038/jcbfm.2009.63.
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Brain edema and swelling is a critical factor in the high mortality and morbidity associated with traumatic brain injury (TBI). Despite this, the mechanisms associated with its development are poorly understood and interventions have not changed in over 30 years. Although neuropeptides and neurogenic inflammation have been implicated in peripheral edema formation, their role in the development of central nervous system edema after brain trauma has not been investigated. This study examines the role of the neuropeptide, substance P (SP), in the development of edema and functional deficits after brain trauma in rats. After severe diffuse TBI in adult male rats, neuronal and perivascular SP immunoreactivity were increased markedly. Perivascular SP colocalized with exogenously administered Evans blue, supporting a role for SP in vascular permeability. Inhibition of SP action by administration of the neurokinin-1 (NIC,) antagonist, N-acetyl-l-tryptophan, at 30 mins after trauma attenuated vascular permeability and edema formation. Administration of the NIC, antagonist also improved both motor and cognitive neurologic outcomes. These findings suggest that SP release is integrally linked to the increased vascular permeability and edema formation after brain trauma, and that treatment with an NIC, receptor antagonist reduces edema and improves neurologic outcome.
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Khavkin, A. I., N. M. Bogdanova, V. P. Novikova, and D. V. Yudina. "Zonulin: physiological and clinical role in the perinatal period." Voprosy ginekologii, akušerstva i perinatologii 19, no. 5 (2020): 132–39. http://dx.doi.org/10.20953/1726-1678-2020-5-132-139.
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Lifestyle change, including diet changes, often lead to an impairment of biological rhythms regulating production of gastrointestinal hormones, enzymes, neuropeptides, and various cytokines that ensure proper functioning of the digestive tract. Such changes are almost always associated with microbiota disorders and increase permeability of the intestinal mucosa. Zonulin is a diagnostic marker regulating intestinal wall stability and modulating the density of intercellular connections. Its biological role and mechanism of action are being actively studied now. This literature review aims to summarize the results of latest studies published over the last five years analyzing the role of zonulin in various diseases and conditions. The article also covers some aspects suggesting that zonulin can be used as a marker of normal functioning of the intestinal barrier not only in therapeutic, but also in obstetric and pediatric practice. Key words: biomarker, inflammatory cytokines, gestation, depression, zonulin, intestinal barrier, metabolism, microbiota, intestinal wall permeability
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Alshagga, Mustafa Ahmed, Mohammed Abdullah Alshawsh, Atefehalsadat Seyedan, Abdulsamad Alsalahi, Yan Pan, Suresh Kumar Mohankumar, Abdolgodose Alkebsi, Saba Kassim, and Zahurin Mohamed. "Khat (Catha edulis) and Obesity: A Scoping Review of Animal and Human Studies." Annals of Nutrition and Metabolism 69, no. 3-4 (2016): 200–211. http://dx.doi.org/10.1159/000452895.
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Background: Khat (Catha edulis) is a plant that is deeply rooted in the cultural life of East African and Southwestern Arabian populations. Prevalent traditional beliefs about khat are that the plant has an effect on appetite and body weight. Summary: This review assesses the accumulated evidences on the mutual influence of monoamines, hormones and neuropeptides that are linked to obesity. A few anti-obesity drugs that exert their mechanisms of action through monoamines are briefly discussed to support the notion of monoamines being a critical target of drug discovery for new anti-obesity drugs. Subsequently, the review provides a comprehensive overview of central dopamine and serotonin changes that are associated with the use of khat or its alkaloids. Then, all the studies on khat that describe physical, biochemical and hormonal changes are summarised and discussed in depth. Conclusion: The reviewed studies provide relatively acceptable evidence that different khat extracts or cathinone produces changes in terms of weight, fat mass, appetite, lipid biochemistry and hormonal levels. These changes are more pronounced at higher doses and long durations of intervention. The most suggested mechanism of these changes is the central action that produces changes in the physiology of dopamine and serotonin. Nonetheless, there are a number of variations in the study design, including species, doses and durations of intervention, which makes it difficult to arrive at a final conclusion about khat regarding obesity, and further studies are necessary in the future to overcome these limitations.
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Dillingham, M. A., and R. J. Anderson. "Mechanism of neuropeptide Y inhibition of vasopressin action in rat cortical collecting tubule." American Journal of Physiology-Renal Physiology 256, no. 3 (March 1, 1989): F408—F413. http://dx.doi.org/10.1152/ajprenal.1989.256.3.f408.
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Neuropeptide Y (NPY) is a unique 36-amino acid peptide found in high concentrations in brain and peripheral neurons. Although NPY is present in kidney tissue, its role in regulation of renal function has not been delineated. We found that NPY significantly decreases arginine vasopressin (AVP) but not adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated hydraulic conductivity (Lp) in perfused rat cortical collecting tubules (CCT). Either alpha 2-adrenergic receptor blockade (yohimbine) or occupancy (clonidine) prevent NPY inhibition of AVP-stimulated Lp. By contrast, alpha 1-adrenergic receptor blockade with prazosin did not alter NPY inhibition of AVP action. Pretreatment of CCT with pertussis toxin also abolishes NPY inhibition of AVP-stimulated Lp. These data suggest that NPY acts via an alpha 2-adrenergic receptor coupled to a pertussis toxin-sensitive protein to inhibit AVP-stimulated cAMP formation and Lp in the rat CCT.
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Conde-Sieira, Marta, Valentina Capelli, Rosa Álvarez-Otero, Adrián Díaz-Rúa, Cristina Velasco, Sara Comesaña, Miguel López, and José L. Soengas. "Hypothalamic AMPKα2 regulates liver energy metabolism in rainbow trout through vagal innervation." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 318, no. 1 (January 1, 2020): R122—R134. http://dx.doi.org/10.1152/ajpregu.00264.2019.
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Hypothalamic AMPK plays a major role in the regulation of whole body metabolism and energy balance. Present evidence has demonstrated that this canonical mechanism is evolutionarily conserved. Thus, recent data demonstrated that inhibition of AMPKα2 in fish hypothalamus led to decreased food intake and liver capacity to use and synthesize glucose, lipids, and amino acids. We hypothesize that a signal of abundance of nutrients from the hypothalamus controls hepatic metabolism. The vagus nerve is the most important link between the brain and the liver. We therefore examined in the present study whether surgical transection of the vagus nerve in rainbow trout is sufficient to alter the effect in liver of central inhibition of AMPKα2. Thus, we vagotomized (VGX) or not (Sham) rainbow trout and then intracerebroventricularly administered adenoviral vectors tagged with green fluorescent protein alone or linked to a dominant negative isoform of AMPKα2. The inhibition of AMPKα2 led to reduced food intake in parallel with changes in the mRNA abundance of hypothalamic neuropeptides [neuropeptide Y ( npy), agouti-related protein 1 ( agrp1), and cocaine- and amphetamine-related transcript ( cartpt)] involved in food intake regulation. Central inhibition of AMPKα2 resulted in the liver having decreased capacity to use and synthesize glucose, lipids, and amino acids. Notably, these effects mostly disappeared in VGX fish. These results support the idea that autonomic nervous system actions mediate the actions of hypothalamic AMPKα2 on liver metabolism. Importantly, this evidence indicates that the well-established role of hypothalamic AMPK in energy balance is a canonical evolutionarily preserved mechanism that is also present in the fish lineage.
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Rose, James D. "Corticosteroid actions from neuronal membrane to behavior: Neurophysiological mechanisms underlying rapid behavioral effects of corticosterone." Biochemistry and Cell Biology 78, no. 3 (April 2, 2000): 307–15. http://dx.doi.org/10.1139/o00-021.
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Investigation of the rapid suppression of male courtship clasping behavior by corticosterone in roughskin newts (Taricha granulosa) has led to the identification of a specific neuronal membrane receptor for this stress steroid. This paper describes studies of the neurophysiological effects of the rapid, membrane receptor mediated action of corticosterone on neurons that are involved in the control of clasping. In freely behaving newts, medullary neurons, including reticulospinal neurons, process clasp-triggering sensory signals and participate in control of clasping movements. Corticosterone injection causes these brainstem neurons to show selective depression of clasping-related sensorimotor function. These corticosterone effects appear in 3-10 min and are closely associated with the simultaneous depression of clasping. In addition to these functionally specific effects, corticosterone simultaneously causes widespread, primarily depressive effects on neuronal activity and excitability in the medulla and elsewhere in the brain. Thus, the membrane actions of corticosterone lead to diverse neural effects, including changes in membrane excitability as well as specific, network-level actions that are apparent only during behavior. These rapid corticosterone effects strongly interact with actions of the neuropeptides vasotocin and corticotropin-releasing factor, such that the form and magnitude of the steroid's effects depend on the prevailing neuroendocrine state of the brain.Key words: glucocorticoid, membrane receptor, non-genomic, amphibian, reproduction.
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Sandeva, Rositsa V., Stanislava M. Mihaylova, and Gergana N. Sandeva. "Leptin And Ghrelin – The New Old Players In Obesity And Depression." Journal of Biomedical and Clinical Research 7, no. 2 (December 1, 2014): 75–80. http://dx.doi.org/10.1515/jbcr-2015-0129.
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Summary The participation of the anorexigenic peptide leptin and the orexigenic peptide ghrelin in the pathogenesis of metabolic syndrome and obesity is well studied. In this review, we are taking a look at the structure, anatomical expression, regulation, receptors and physiological functions of these two neuropeptides. Leptin is produced almost exclusively in adipose tissue. It acts on the brain and is a key element in long-term regulation of energy balance. Leptin suppresses appetite and reduces body weight. Besides its central effects, important aspects of its action on peripheral tissues have been discovered recently: direct regulation of immune cells, pancreatic beta cells, adipocytes and muscle cells. Ghrelin is an endogenous ligand for the active form of the growth hormone receptor (GHS-R1a) and stimulates food intake and growth hormone secretion. We focus on the role of leptin and ghrelin in central nervous system neural mechanisms that are associated with depression. Studying new aspects of these two neuropeptides aims to expand our knowledge of the pathogenesis and therapeutic approaches to diseases with which they are associated: obesity, depression, type 2 diabetes, essential hypertension, and more.
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Borson, D. B. "Roles of neutral endopeptidase in airways." American Journal of Physiology-Lung Cellular and Molecular Physiology 260, no. 4 (April 1, 1991): L212—L225. http://dx.doi.org/10.1152/ajplung.1991.260.4.l212.
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In recent years, studies of the regulation of the airways have focused to an increasing degree on the roles of neuropeptides. Several peptides have been shown to be present in airways and mediate such diverse responses as ion transport, mucus secretion, bronchospasm or relaxation, edema, cough, changes in vascular permeability, and neutrophil chemotaxis. More recently, studies have described the roles of peptidases, most notably neutral endopeptidase (NEP, also known as enkephalinase, or E.C. 3.4.24.11) and kininase II (also known as angiotensin-converting enzyme, or E.C. 3.4.15.1) in modulating peptide-induced responses. The enzymes cleave a wide variety of peptides, generating metabolites that are inactive in the systems studied to date. Thus inhibitors of NEP potentiate responses to peptides that are cleaved by it. Therefore, NEP plays roles in modulating peptide-induced effects analogous to the role of acetylcholinesterase in modulating cholinergic neurotransmission. In several experimental respiratory diseases, the activity of neutral endopeptidase is decreased, resulting in increased responses to peptides. The therapeutic application of recombinant NEP protects the airways from the adverse actions of stimuli that release inflammatory peptides, and induction of the NEP gene expression by glucocorticoids suggest a possible mechanism for the action of these steroids in treating airway diseases such as asthma, chronic bronchitis, or cystic fibrosis.
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Humphrey, PPA, and PJ Goadsby. "The Mode of Action of Sumatriptan is Vascular? A Debate." Cephalalgia 14, no. 6 (December 1994): 401–10. http://dx.doi.org/10.1046/j.1468-2982.1994.1406401.x.
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Two mechanisms have been proposed to explain the primary mode of action of sumatriptan: vasoconstriction, and trigeminal nerve terminal inhibition. Sumatriptan is a potent vasoconstrictor of intracranial arteries. It has been shown to increase blood flow velocity in large intracranial arteries in man in a dose-dependent fashion both during and between migraine attacks. Since the vasoconstrictor response of sumatriptan is reproducible outside the migraine attack, this action appears to be a direct vascular effect and not indirectly mediated via neural mechanisms. Sumatriptan also causes rapid constriction of dural and meningeal vessels in vivo. It does not modify cerebral blood flow but does constrict arteriovenous anastamoses that may be dilated during a migraine attack. This evidence suggests that sumatriptan has a direct, dose-related, vasoconstrictor action on certain intracranial blood vessels that correlates with its antimigraine activity. Alternatively, sumatriptan may act directly on the trigeminal sensory nerve terminals within the cranial blood vessel, inhibiting the release of sensory neuropeptides. Experimental data from animal studies have shown that following electrical stimulation of the trigeminal ganglion there is a neurogenic inflammatory response with plasma protein extravasation from dural blood vessels. This response can be significantly reduced by sumatriptan at a dose level similar to that used in clinical treatment. This finding is further supported by the clinical observation that sumatriptan reduces the plasma levels of calcitonin gene-related peptide which are raised during a migraine attack.
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Dhillo, Waljit S., Caroline J. Small, Preeti H. Jethwa, Sabina H. Russell, James V. Gardiner, Gavin A. Bewick, Asha Seth, Kevin G. Murphy, Mohammad A. Ghatei, and Stephen R. Bloom. "Paraventricular Nucleus Administration of Calcitonin Gene-Related Peptide Inhibits Food Intake and Stimulates the Hypothalamo-Pituitary-Adrenal Axis." Endocrinology 144, no. 4 (April 1, 2003): 1420–25. http://dx.doi.org/10.1210/en.2002-220902.
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Abstract Calcitonin gene-related protein (CGRP) inhibits food intake and stimulates the hypothalamo-pituitary-adrenal (HPA) axis after intracerebroventricular injection in rats. However, the hypothalamic site and mechanism of action are unknown. We investigated the effects of intraparaventricular nucleus administration (iPVN) of CGRP on food intake and the HPA axis in rats and the effect of CGRP on the release of hypothalamic neuropeptides in vitro. In addition, we investigated the effects of food deprivation on hypothalamic CGRP expression. CGRP dose-dependently reduced food intake in the first hour after iPVN injection in fasted male rats (saline, 5.1 ± 0.8 g; 0.3 nmol CGRP, 1.1 ± 0.5 g; P < 0.001 vs. saline). iPVN injection of CGRP8–37 (a CGRP1 receptor antagonist) alone had no effect on food intake. However, the reduction in food intake by iPVN CGRP was attenuated by prior administration of CGRP8–37 [CGRP8–37 (10 nmol)/CGRP (0.3 nmol), 3.0 ± 0.8 g; P < 0.05 vs. 0.3 nmol CGRP]. CGRP (100 nm) stimulated the release of α-melanocyte stimulating hormone, cocaine- and amphetamine-related transcript, corticotropin-releasing hormone, and arginine vasopressin from hypothalamic explants to 127 ± 19%, 148 ± 10%, 158 ± 17%, and 198 ± 21% of basal levels, respectively (P < 0.05 vs. basal), but did not alter the release of either neuropeptide Y or agouti-related protein. Hypothalamic CGRP mRNA levels in 24-h fasted rats were increased to 130 ± 8% of control levels [CGRP mRNA (arbitrary units), 4.75 ± 0.4; controls, 3.65 ± 0.34; P < 0.05]. Our data suggest that CGRP administered to the PVN inhibits food intake and stimulates the HPA axis.
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Seckl, M. J., A. Weinglass, and Q. Li. "The molecular mechanism of action of substance P (SP) analogue broad spectrum neuropeptide antagonists." Lung Cancer 29, no. 1 (September 2000): 191–92. http://dx.doi.org/10.1016/s0169-5002(00)80647-9.
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Colmers, WF, K. Lukowiak, and QJ Pittman. "Neuropeptide Y action in the rat hippocampal slice: site and mechanism of presynaptic inhibition." Journal of Neuroscience 8, no. 10 (October 1, 1988): 3827–37. http://dx.doi.org/10.1523/jneurosci.08-10-03827.1988.
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Pineda, R., D. Garcia-Galiano, M. A. Sanchez-Garrido, M. Romero, F. Ruiz-Pino, E. Aguilar, F. A. Dijcks, et al. "Characterization of the Potent Gonadotropin-Releasing Activity of RF9, a Selective Antagonist of RF-Amide-Related Peptides and Neuropeptide FF Receptors: Physiological and Pharmacological Implications." Endocrinology 151, no. 4 (February 16, 2010): 1902–13. http://dx.doi.org/10.1210/en.2009-1259.
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Identification of RF-amide-related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone, has drawn considerable interest on its potential effects and mechanisms of action in the control of gonadotropin secretion in higher vertebrates. Yet, these analyses have so far relied mostly on indirect approaches, while direct assessment of their physiological roles has been hampered by the lack of suitable antagonists. RF9 was recently reported as a selective and potent antagonist of the receptors for RFRP (RFRPR) and the related neuropeptides, neuropeptide FF (NPFF) and neuropeptide AF (NPFF receptor). We show here that RF9 possesses very strong gonadotropin-releasing activities in vivo. Central administration of RF9 evoked a dose-dependent increase of LH and FSH levels in adult male and female rats. Similarly, male and female mice responded to intracerebroventricular injection of RF9 with robust LH secretory bursts. In rats, administration of RF9 further augmented the gonadotropin-releasing effects of kisspeptin, and its stimulatory effects were detected despite the prevailing suppression of gonadotropin secretion by testosterone or estradiol. In fact, blockade of estrogen receptor-α partially attenuated gonadotropin responses to RF9. Finally, systemic administration of RF9 modestly stimulated LH secretion in vivo, although no direct effects in terms of gonadotropin secretion were detected at the pituitary in vitro. Altogether, these data are the first to disclose the potent gonadotropin-releasing activity of RF9, a selective antagonist of RFRP (and NPFF) receptors. Our findings support a putative role of the RFRP/gonadotropin-inhibitory hormone system in the central control of gonadotropin secretion in mammals and have interesting implications concerning the potential therapeutic indications and pharmacological effects of RF9.
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Mathé, Aleksander A., Henriette Husum, Aram El Khoury, Patricia Jiménez-Vasquez, Susanne H. M. Gruber, Gitta Wörtwein, Georg Nikisch, et al. "Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role?" Physiology & Behavior 92, no. 1-2 (September 2007): 226–31. http://dx.doi.org/10.1016/j.physbeh.2007.05.016.
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McDonald, John L., Allan W. Cripps, Peter K. Smith, Caroline A. Smith, Charlie C. Xue, and Brenda Golianu. "The Anti-Inflammatory Effects of Acupuncture and Their Relevance to Allergic Rhinitis: A Narrative Review and Proposed Model." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/591796.
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Classical literature indicates that acupuncture has been used for millennia to treat numerous inflammatory conditions, including allergic rhinitis. Recent research has examined some of the mechanisms underpinning acupuncture's anti-inflammatory effects which include mediation by sympathetic and parasympathetic pathways. The hypothalamus-pituitary-adrenal (HPA) axis has been reported to mediate the antioedema effects of acupuncture, but not antihyperalgesic actions during inflammation. Other reported anti-inflammatory effects of acupuncture include an antihistamine action and downregulation of proinflammatory cytokines (such as TNF-α, IL-1β, IL-6, and IL-10), proinflammatory neuropeptides (such as SP, CGRP, and VIP), and neurotrophins (such as NGF and BDNF) which can enhance and prolong inflammatory response. Acupuncture has been reported to suppress the expression of COX-1, COX-2, and iNOS during experimentally induced inflammation. Downregulation of the expression and sensitivity of the transient receptor potential vallinoid 1 (TRPV1) after acupuncture has been reported. In summary, acupuncture may exert anti-inflammatory effects through a complex neuro-endocrino-immunological network of actions. Many of these generic anti-inflammatory effects of acupuncture are of direct relevance to allergic rhinitis; however, more research is needed to elucidate specifically how immune mechanisms might be modulated by acupuncture in allergic rhinitis, and to this end a proposed model is offered to guide further research.
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Poulat, Philippe, Jacques Champlain, and Réjean Couture. "Cardiovascular responses to intrathecal neuropeptide γ in conscious rats: receptor characterization and mechanism of action." British Journal of Pharmacology 117, no. 2 (January 1996): 250–57. http://dx.doi.org/10.1111/j.1476-5381.1996.tb15184.x.
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Hsieh, Y. S., P. N. Chen, C. H. Yu, and D. Y. Kuo. "Central dopamine action modulates neuropeptide-controlled appetite via the hypothalamic PI3K/NF-κB-dependent mechanism." Genes, Brain and Behavior 13, no. 8 (September 19, 2014): 784–93. http://dx.doi.org/10.1111/gbb.12174.
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Kurzanov, A. N., and I. M. Bykov. "NEUROMODULATOR LIGAND-RECEPTOR SYSTEM TIP39 - PTH2R." Crimea Journal of Experimental and Clinical Medicine 10, no. 2 (2020): 78–85. http://dx.doi.org/10.37279/2224-6444-2020-10-2-78-85.
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Widely spread axon terminals of TIP39 neurons have a distribution similar to PTH2R containing neurons and their fibers which provides an anatomic base of neuromodulation action of TIP39. This functional and anatomic link- ing lets state that TIP39 and PTH2R form a neuromodulator ligand-receptor system. Basing on mechanisms of signal transmission used by TIP39 and PTH2R, they can form a neuromodulator system in many brain parts. TIP39-PTH2R system is a unique neuropeptide-receptor system, which localization and functions in the central nervous system differ from any other neuropeptides. Neuromodulator system TIP39-PTH2R predominantly participates in neuroendocrinal modulation by affecting the endocrinal system by means of its presence in several areas of hypothalamus. TIP39 influences neurons that contain somatostatin and corticotropin-releasing hormone. TIP39 can affect the release of adrenocorticotropin, luteinizing hormone, growth hormone and arginine-vasopressin from hypophysis. Experimental data prove that TIP39 modulates regulatory network of anxiety and depression, several aspects of stress reaction and also controls body temperature, participates in processing of auditory and nociceptive information. Physiological role of TIP39-PTH2R system is still to some extent unknown. However, distribution of PTH2R and TIP39 in tissues outside central nervous system assumes other potential physiological effects for this signal way. It is assumed that TIP39- PTH2R system should be probably considered as a potential therapeutic target for treatment of anxiety, depression and chronic pain, control and correction of neuroendocrine disruptions.