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1
Shariati, G. H., G. Ahangari, M. R. Asadi, F. Poyafard, and H. R. Ahmadkhaniha. "Dopamine Receptor Gene Expression Changes in Peripheral Blood Mononuclear Cells from Schizophrenic Patients Treated with Haloperidol and Olanzapine." European Journal of Inflammation 7, no. 2 (May 2009): 71–76. http://dx.doi.org/10.1177/1721727x0900700203.
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We investigated dopamine receptor gene expression in peripheral blood mononuclear cells of schizophrenic patients before and after treatment. Also dopamine receptor genes expression profile was compared in two treatment groups including haloperidol and olanzapine. The peripheral blood mononuclear cells were separated from whole blood by Ficoll-hypaque; the total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time polymerase chain reaction using primer pairs specific for five dopamine receptor mRNAs and β-actin as internal control. The results show the presence of all types of dopamine receptor in lymphocytes. Dopamine receptor gene expression profile in dopamine receptor D2 gene and dopamine receptor D4 gene showed significant changes that were correlated with the type of treatment and Clinical Global Impressions score improvement. In conclusion, the present study shows that human lymphocytes express dopamine receptor D1–D5 genes. Moreover, investigated dopamine receptors gene expression in peripheral blood mononuclear cells of schizophrenic patients correlated with clinical symptom improvement.
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Sarkar, D. K., K. Chaturvedi, S. Oomizu, N. I. Boyadjieva, and C. P. Chen. "Dopamine, Dopamine D2 Receptor Short Isoform, Transforming Growth Factor (TGF)-β1, and TGF-β Type II Receptor Interact to Inhibit the Growth of Pituitary Lactotropes." Endocrinology 146, no. 10 (October 1, 2005): 4179–88. http://dx.doi.org/10.1210/en.2005-0430.
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The neurotransmitter dopamine is known to inhibit prolactin secretion and the proliferation of lactotropes in the pituitary gland. In this study, we determined whether dopamine and TGFβ1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGFβ1 secretion and TGFβ1 mRNA expression but inhibited lactotropic cell proliferation both in vivo and in vitro. The dopamine’s inhibitory action on lactotropic cell proliferation was blocked by a TGFβ1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGFβ1 type II receptor and TGFβ1 mRNA levels and had undetectable levels of TGFβ1 protein. These cells showed a reduced TGFβ1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGFβ1 and TGFβ1 type II receptor gene expression and recovered dopamine- and TGFβ1-induced growth inhibition in PR1 cells. The constitutive expression of D2 receptor short isoform also reduced the tumor cell growth rate. These data suggest that a TGFβ1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.
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Peiser, Christian, Marcello Trevisani, David A. Groneberg, Q. Thai Dinh, Doerthe Lencer, Silvia Amadesi, Barbara Maggiore, Selena Harrison, Pierangelo Geppetti, and Axel Fischer. "Dopamine type 2 receptor expression and function in rodent sensory neurons projecting to the airways." American Journal of Physiology-Lung Cellular and Molecular Physiology 289, no. 1 (July 2005): L153—L158. http://dx.doi.org/10.1152/ajplung.00222.2004.
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Agonists of the dopamine receptors have been demonstrated to have bronchodilatory properties in pathologically constricted airways. The mechanism by which these agonists induce bronchodilatation is thought to involve airway sensory nerves. In this study, the expression and function of dopamine D2 receptor were examined in sensory ganglia supplying the airways. Neuronal dopamine D2 receptor mRNA expression was demonstrated by single-cell RT-PCR following laser-assisted microdissection. The projection of the neurons to the airways was confirmed by retrograde neuronal labeling. In functional studies, dopamine D2 receptor agonists (AR-C65116AB and ropinirole) inhibited intraneuronal calcium mobilization in rat capsaicin-sensitive primary sensory neurons and capsaicin-induced plasma extravasation in the rat trachea. Our results provide support to the hypothesis that dopamine D2 receptor activation inhibits neurogenic inflammation and proinflammatory reflex responses.
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Myslivecek, Jaromir. "Dopamine and Dopamine-Related Ligands Can Bind Not Only to Dopamine Receptors." Life 12, no. 5 (April 19, 2022): 606. http://dx.doi.org/10.3390/life12050606.
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The dopaminergic system is one of the most important neurotransmitter systems in the central nervous system (CNS). It acts mainly by activation of the D1-like receptor family at the target cell. Additionally, fine-tuning of the signal is achieved via pre-synaptic modulation by the D2-like receptor family. Some dopamine drugs (both agonists and antagonists) bind in addition to DRs also to α2-ARs and 5-HT receptors. Unfortunately, these compounds are often considered subtype(s) specific. Thus, it is important to consider the presence of these receptor subtypes in specific CNS areas as the function virtually elicited by one receptor type could be an effect of other—or the co-effect of multiple receptors. However, there are enough molecules with adequate specificity. In this review, we want to give an overview of the most common off-targets for established dopamine receptor ligands. To give an overall picture, we included a discussion on subtype selectivity. Molecules used as antipsychotic drugs are reviewed too. Therefore, we will summarize reported affinities and give an outline of molecules sufficiently specific for one or more subtypes (i.e., for subfamily), the presence of DR, α2-ARs, and 5-HT receptors in CNS areas, which could help avoid ambiguous results.
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Helms, My N., Xi-Juan Chen, Semra Ramosevac, Douglas C. Eaton, and Lucky Jain. "Dopamine regulation of amiloride-sensitive sodium channels in lung cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 290, no. 4 (April 2006): L710—L722. http://dx.doi.org/10.1152/ajplung.00486.2004.
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Dopamine increases lung fluid clearance. This is partly due to activation of basolateral Na-K-ATPase. However, activation of Na-K-ATPase by itself is unlikely to produce large changes in transepithelial transport. Therefore, we examined apical and basolateral dopamine's effect on apical, highly selective sodium channels [epithelial sodium channels (ENaC)] in monolayers of an alveolar type 2 cell line (L2). Dopamine increased channel open probability ( Po) without changing the unitary current. The D1 receptor blocker SCH-23390 blocked the dopamine effect, but the D2 receptor blocker sulpiride did not. The dopamine-mediated increase in ENaC activity was not a secondary effect of dopamine stimulation of Na-K-ATPase, since ouabain applied to the basolateral surface to block the activity of Na-K-ATPase did not alter dopamine-mediated ENaC activity. Protein kinase A (PKA) was not responsible for dopamine's effect since a PKA inhibitor, H89, did not reduce dopamine's effect. However, cpt-2-O-Me-cAMP, which selectively binds and activates EPAC (exchange protein activated by cAMP) but not PKA, increased ENaC Po. An Src inhibitor, PP2, and the phosphatidylinositol-3-kinase inhibitor, LY-294002, blocked dopamine's effect on ENaC. In addition, an MEK blocker, U0126, an inhibitor of phospholipase A2, and a protein phosphatase inhibitor also blocked the effect of dopamine on ENaC Po. Finally, since the cAMP-EPAC-Rap1 pathway also activates DARPP32 (32-kDa dopamine response protein phosphatase), we confirmed that dopamine phosphorylates DARPP32, and okadaic acid, which blocks phosphatases (DARPP32), also blocks dopamine's effect. In summary, dopamine increases ENaC activity by a cAMP-mediated alternative signaling pathway involving EPAC and Rap1, signaling molecules usually associated with growth-factor-activated receptors.
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Ding, Guoliang, Rob F. Wiegerinck, Ming Shen, Anca Cojoc, Carlo M. Zeidenweber, and Mary B. Wagner. "Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and β2 receptors." American Journal of Physiology-Heart and Circulatory Physiology 294, no. 5 (May 2008): H2327—H2335. http://dx.doi.org/10.1152/ajpheart.00993.2007.
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Dopamine is used to treat heart failure, particularly after cardiac surgery in infants, but the mechanisms of action are unclear. We investigated differences in the effect of dopamine on L-type calcium current ( ICa) between newborn (NB, 1–4 days) and adult (AD, 3–4 mo) rabbit ventricular myocytes. Myocytes were enzymatically dissociated from NB and AD rabbit hearts. ICa was recorded by using the whole cell patch-clamp technique. mRNA levels of cardiac dopamine receptor type 1 (D1), type 2 (D2), and β-adrenergic receptors (β-ARs) were measured by real-time RT-PCR. Dopamine (100 μM) increased ICa more in NB (Emax 87 ± 10%) than in AD ventricular cells (Emax 21 ± 3%). Further investigation of this difference showed that mRNA levels of the D1 receptor were significantly higher in NB, and, with β-AR blockade, dopamine increased ICa more in NB than AD cells. Additionally, SKF-38393 (selective D1 receptor agonist) significantly increased ICa by 55 ± 4% in NB ( P < 0.05, n = 4) and by 11 ± 1% in AD ( P < 0.05, n = 6). Dopamine in the presence of SCH-23390 (D1 receptor antagonist) increased ICa in NB cells by 67 ± 5% and by 22 ± 2% in AD cells, suggesting a role for β-AR stimulation. Selective blockade of β1- or β2-receptors (with block of D1 receptors) showed that the β-AR action of dopamine in the NB was largely mediated via β2-AR activation. Dopamine produces a larger increase in ICa in NB cardiomyocytes compared with ADs. The mechanism of action is not only through β2-ARs but also due to higher expression of cardiac D1 receptor in NB.
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MORA-FERRER, CARLOS, and VOLKER GANGLUFF. "D2-dopamine receptor blockade impairs motion detection in goldfish." Visual Neuroscience 17, no. 2 (March 2000): 177–86. http://dx.doi.org/10.1017/s0952523800171196.
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Under photopic illumination conditions, motion detection in goldfish is dominated by the long-wavelength-sensitive cone type (L-cone), and under scotopic conditions motion it is determined by rods (Schaerer & Neumeyer, 1996). The switch from rod-dominated to cone-dominated motion detection occurs during light adaptation. It has been suggested that dopamine acts as a neuronal light-adaptative signal. It is known that dopamine affects wavelength discrimination through D1-dopamine receptors (Mora-Ferrer & Neumeyer, 1996), and the dorsal light reflex through D1- and D2-dopamine receptors (Lin & Yazulla, 1994a). The purpose of this study was to determine whether dopamine influenced movement detection by goldfish, and if so, which dopamine receptor was involved. The D2-dopamine receptor antagonist sulpiride reduced the animal's sensitivity to the moving stimulus, whereas SCH 23390, a D1-dopamine receptor antagonist, did not have any effect. The effect of sulpiride is discussed in relation to known sulpiride effects on retinal neurons and the retinal pigment epithelium.
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Hayashida, Yuki, and Andrew T. Ishida. "Dopamine Receptor Activation Can Reduce Voltage-Gated Na+ Current by Modulating Both Entry Into and Recovery From Inactivation." Journal of Neurophysiology 92, no. 5 (November 2004): 3134–41. http://dx.doi.org/10.1152/jn.00526.2004.
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We tested whether dopamine receptor activation modulates the voltage-gated Na+ current of goldfish retinal ganglion cells, using a fast voltage-clamp amplifier, perforated-patch whole cell mode, and a physiological extracellular Na+ concentration. As found in other cells, activators of D1-type dopamine receptors and of protein kinase A reduced the amplitude of current activated by depolarizations from resting potential without altering the current kinetics or activation range. However, D1-type dopamine receptor activation also accelerated the rate of entry into inactivation during subthreshold depolarizations and slowed the rate of recovery from inactivation after single, brief depolarizations. Our results provide the first evidence in any preparation that D1-type receptor activation can produce both of these latter effects.
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Pfeiffer-Linn, C., and E. M. Lasater. "Dopamine modulates in a differential fashion T- and L-type calcium currents in bass retinal horizontal cells." Journal of General Physiology 102, no. 2 (August 1, 1993): 277–94. http://dx.doi.org/10.1085/jgp.102.2.277.
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White bass (Roccus chrysops) retinal horizontal cells possess two types of voltage-activated calcium currents which have recently been characterized with regard to their voltage dependence and pharmacology (Sullivan, J., and E. M. Lasater. 1992. Journal of General Physiology. 99:85-107). A low voltage-activated transient current was identified which resembles the T-type calcium current described in a number of other preparations, along with a sustained high threshold, long-lasting calcium current that resembles the L-type calcium current. Here we report on the modulation of horizontal cell calcium channels by dopamine. Under whole-cell voltage clamp conditions favoring the expression of both calcium currents, dopamine had opposing actions on the two types of voltage-sensitive calcium currents in the same cone-type horizontal cell. The L-type calcium current was significantly potentiated by dopamine while the T-type current was simultaneously reduced. Dopamine had no effect on calcium currents in rod-type horizontal cells. Both of dopamine's actions were mimicked with the D1 receptor agonist, SKF 38393, and blocked by application of the D1 specific antagonist, SCH 23390. Dopamine's actions on the two types of calcium currents in white bass horizontal cells are mimicked by the cell membrane-permeant cyclic AMP derivative, 8-(4-chlorophenylthio)-cyclic AMP, suggesting that dopamine's action is linked to a cAMP-mediated second messenger system. Furthermore, the inhibitor of cAMP-dependent protein kinase blocked both of dopamine's actions on the voltage-dependent calcium channels when introduced through the patch pipette. This indicates that protein phosphorylation is involved in modulating horizontal cell calcium channels by dopamine. Taken together, these results show that dopamine has differential effects on the voltage-dependent calcium currents in retinal horizontal cells. The modulation of these currents may play a role in shaping the response properties of horizontal cells.
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Milienne-Petiot, Morgane, Lucianne Groenink, Arpi Minassian, and Jared W. Young. "Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels." Journal of Psychopharmacology 31, no. 10 (September 27, 2017): 1334–46. http://dx.doi.org/10.1177/0269881117731162.
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Background: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D1-family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Methods: Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D1-family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Results: Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Conclusions: Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D1-family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D1-family receptors supports the hypothesis that D1 and/or D5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.
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Pedarzani, P., and J. F. Storm. "Dopamine modulates the slow Ca(2+)-activated K+ current IAHP via cyclic AMP-dependent protein kinase in hippocampal neurons." Journal of Neurophysiology 74, no. 6 (December 1, 1995): 2749–53. http://dx.doi.org/10.1152/jn.1995.74.6.2749.
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1. The effects of dopamine on the slow Ca(2+)-dependent K+ current (IAHP; AHP, afterhyperpolarization) and spike frequency adaptation were studied by whole cell voltage-clamp and sharp microelectrode current-clamp recordings in rat CA1 pyramidal neurons in rat hippocampal slices. 2. Dopamine suppressed IAHP in a dose-dependent manner, under whole cell voltage-clamp conditions. Similarly, under current-clamp conditions, dopamine inhibited spike frequency adaptation and suppressed the slow afterhyperpolarization. 3. The effect of dopamine on IAHP was mimicked by a D1 receptor agonist and blocked by dopamine receptor antagonists only in a minority of the cells. 4. Dopamine suppressed IAHP after blocking or desensitizing the beta-adrenergic receptors and, hence, did not act by cross-reacting with this receptor type. 5. The effects of dopamine on IAHP and spike frequency adaptation were suppressed by blocking the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent kinase (PKA) with Rp-cAMPS and, hence, are probably mediated by the activation of this kinase. 6. We conclude that dopamine increases hippocampal neuron excitability, like other monoamine neurotransmitters, by suppressing IAHP and spike frequency adaptation, via cAMP and protein kinase A. The receptor type mediating this effect of dopamine remains to be defined.
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Garcia-Garrote, Maria, Juan A. Parga, Pablo J. Labandeira, Jose Luis Labandeira-Garcia, and Jannette Rodriguez-Pallares. "Dopamine Regulates Adult Neurogenesis in the Ventricular-Subventricular Zone via Dopamine D3 Angiotensin Type 2 Receptor Interactions." Stem Cells 39, no. 12 (September 20, 2021): 1778–94. http://dx.doi.org/10.1002/stem.3457.
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Abstract Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesis.
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Yan, Zhen, Wen-Jie Song, and D. James Surmeier. "D2 Dopamine Receptors Reduce N-Type Ca2+ Currents in Rat Neostriatal Cholinergic Interneurons Through a Membrane-Delimited, Protein-Kinase-C-Insensitive Pathway." Journal of Neurophysiology 77, no. 2 (February 1, 1997): 1003–15. http://dx.doi.org/10.1152/jn.1997.77.2.1003.
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Yan, Zhen, Wen-Jie Song, and D. James Surmeier. D2 dopamine receptors reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein-kinase-C-insensitive pathway. J. Neurophysiol. 77: 1003–1015, 1997. Dopamine has long been known to regulate the activity of striatal cholinergic interneurons and the release of acetylcholine. Yet, the cellular mechanisms by which this regulation occurs have not been elucidated. One way in which dopamine might act is by modulating voltage-dependent Ca2+ channels. To test this hypothesis, the impact of dopaminergic agonists on Ca2+ channels in neostriatal cholinergic interneurons was studied by combined whole cell voltage-clamp recording and single-cell reverse transcription–polymerase chain reactions. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. Nearly all interneurons tested (90%, n = 17) coexpressed D2 (short and long isoforms) and D1b (D5) dopamine receptor mRNAs. D1a receptor mRNA was found in only a small subset (20%) of the sample and D3 and D4 receptor mRNAs were undetectable. D2 receptor agonists rapidly and reversibly reduced N-type Ca2+ currents. D1b/D1a receptor activation had little or no effect on Ca2+ currents. The D2 receptor antagonist sulpiride blocked the effect of D2 agonists. Dialysis with guanosine-5′-O-(2-thiodiphosphate) or brief exposure to the G protein (Gi/o) alkylating agent N-ethylmaleimide also blocked the D2 modulation. The reduction in N-type currents was neither accompanied by kinetic slowing nor significantly reversed by depolarizing prepulses. The D2 receptor effects were mediated by a membrane-delimited pathway, because the modulation was not seen in cell-attached patches when agonist was applied to the bath and was not disrupted by perturbations in cytosolic signaling pathways known to be linked to D2 receptors. Activation of M2 muscarinic receptors occluded the D2 modulation, suggesting a shared signaling element. However, activation of protein kinase C attenuated the M2 modulation without significantly affecting the D2 modulation. Taken together, our results suggest that activation of D2 dopamine receptors in cholinergic interneurons reduces N-type Ca2+ currents via a membrane-delimited, Gi/o class G protein pathway that is not regulated by protein kinase C. This signaling pathway may underlie the ability of D2 receptors to reduce striatal acetylcholine release.
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Ahangari, G., G. H. Shariati, M. R. Asadi, M. R. Ostadali, and H. R. Ahmadkhaniha. "Novel Mutation Detection of Regulatory Molecule Dopamine Gene Receptors (D1–D5) Encoding Analysis on Human Peripheral Blood Lymphocytes in Schizophrenia Patients." European Journal of Inflammation 7, no. 3 (September 2009): 145–52. http://dx.doi.org/10.1177/1721727x0900700304.
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There is much evidence which highlights the involvement of the dopamine system in the pathophysiology of schizophrenia. Recently, there have been reports of detected mutations in dopamine gene receptors in genomic DNA of schizophrenia. In this study, we attempt to determine whether there is mutation in encoding dopamine receptor. The PBMC was separated from whole blood by Ficoll-hypaque; the total cellular RNA was extracted and the cDNA was synthesized. This process followed by real-time PCR using primer pairs specific for five dopamine receptor mRNAs and β-actin as internal control. The results show the presence of all types of dopamine receptor types in lymphocytes. The mutational analysis of the obtained PCR products for the respective dopamine receptor fragments were analyzed by sequenced capillary system. The results presented in this study confirm the high frequency of mutations in dopamine gene receptor DRD5 in schizophrenia patients. Mutational amino acid changes in dopamine gene receptors of DR2, DR3, DR4 but not DR1 are also shown. In conclusion, this is the first report of such complete mutational analyses in all dopamine gene receptors. Moreover, we found new mutations and 80% frequency of mutations in DRD5. These data further strengthen the argument for the role of dopamine gene receptor mutations in the pathogenesis of schizophrenia.
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Tomassoni, Daniele, Enea Traini, Manuele Mancini, Vincenzo Bramanti, Syed Sarosh Mahdi, and Francesco Amenta. "Dopamine, vesicular transporters, and dopamine receptor expression in rat major salivary glands." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, no. 5 (September 2015): R585—R593. http://dx.doi.org/10.1152/ajpregu.00455.2014.
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The localization of dopamine stores and the expression and localization of dopamine (DAT) and vesicular monoamine transporters (VMAT) type-1 and -2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat submandibular, sublingual, and parotid salivary glands by HPLC with electrochemical detection, as well as immunochemical and immunohistochemical techniques. Male Wistar rats of 2 mo of age were used. The highest dopamine levels were measured in the parotid gland, followed by the submandibular and sublingual glands. Western blot analysis revealed DAT, VMAT-1, VMAT-2, and dopamine receptors immunoreactivity in membrane preparations obtained from the three glands investigated. Immunostaining for dopamine and transporters was developed within striated ducts. Salivary glands processed for dopamine receptors immunohistochemistry developed an immunoreaction primarily in striated and excretory ducts. In the submandibular gland, acinar cells displayed strong immunoreactivity for the D2 receptor, while cells of the convoluted granular tubules were negative for both D1-like and D2-like receptors. Parotid glands acinar cells displayed the highest immunoreactivity for both D1 and D2 receptors compared with other salivary glands. The above localization of dopamine and dopaminergic markers investigated did not correspond closely with neuron-specific enolase (NSE) localization. This indicates that at least in part, catecholamine stores and dopaminergic markers are independent from glandular innervation. These findings suggest that rat major salivary glands express a dopaminergic system probably involved in salivary secretion. The stronger immunoreactivity for dopamine transporters and receptors in striated duct cells suggests that the dopaminergic system could regulate not only quality, but also volume and ionic concentration of saliva.
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Kalinnikova, Tatiana Borisovna, Rufina Rifkatovna Kolsanova, Evgenia Borisovna Belova, Dilyara Makhmutrievna Khakimova, Marat Khamitovich Gainutdinov, and Rifgat Roaldovich Shagidullin. "The possible role of dopamine receptors DOP-1 and DOP-3 in behavior thermotolerance regulation of Caenorhabditis elegans Maupas." Samara Journal of Science 7, no. 2 (June 15, 2018): 63–68. http://dx.doi.org/10.17816/snv201872112.
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The paper investigates dopamine influence on the tolerance of swimming, induced by mechanical stimulus, to the temperature of 36C during the experiments with nematodes of wild type strain N2 and mutant strains LX636 ( dop-1 ( vs101 )) and LX703 ( dop-3 ( vs106 )) with null-mutations of genes of dopamine receptors DOP-1 and DOP-3. The authors have shown that dopamine in concentrations 0,5-1,0 mM increased the behavior thermotolerance of C. elegans while in concentrations 7,5-15,0 dopamine caused its decrease. Null-mutation of dopamine receptor gene dop-3 prevented the decrease of C. elegans thermotolerance by dopamine. On the contrary, null-mutation of dopamine receptor gene dop-1 caused significant rise in sensitivity of behavior thermotolerance to dopamine. In connection with well-known conceptions assuming that the reason of heat damage of C. elegans behavior is acetylcholine deficiency due to inhibition of its secretion by hyperthermia, the dopamine influence on behavior thermotolerance can be accounted for the dopamine influence on acetylcholine secretion by motor neurons. It is known that in C. elegans motor neurons the coexpression of genes of receptors DOP-1 and DOP-3 takes place. Activation of these receptors in turn causes opposite changes in dopamine secretion.
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Hegg, Colleen C., and Mary T. Lucero. "Dopamine Reduces Odor- and Elevated-K+-Induced Calcium Responses in Mouse Olfactory Receptor Neurons In Situ." Journal of Neurophysiology 91, no. 4 (April 2004): 1492–99. http://dx.doi.org/10.1152/jn.00670.2003.
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Although D2 dopamine receptors have been localized to olfactory receptor neurons (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in ORNs, dopaminergic modulation of either odor responses or excitability in mammalian ORNs has not previously been demonstrated. We found that <50 μM dopamine reversibly suppresses odor-induced Ca2+ transients in ORNs. Confocal laser imaging of 300-μm-thick slices of neonatal mouse olfactory epithelium loaded with the Ca2+-indicator dye fluo-4 AM revealed that dopaminergic suppression of odor responses could be blocked by the D2 dopamine receptor antagonist sulpiride (<500 μM). The dopamine-induced suppression of odor responses was completely reversed by 100 μM nifedipine, suggesting that D2 receptor activation leads to an inhibition of L-type Ca2+ channels in ORNs. In addition, dopamine reversibly reduced ORN excitability as evidenced by reduced amplitude and frequency of Ca2+ transients in response to elevated K+, which activates voltage-gated Ca2+ channels in ORNs. As with the suppression of odor responses, the effects of dopamine on ORN excitability were blocked by the D2 dopamine receptor antagonist sulpiride (<500 μM). The observation of dopaminergic modulation of odor-induced Ca2+ transients in ORNs adds to the growing body of work showing that olfactory receptor neurons can be modulated at the periphery. Dopamine concentrations in nasal mucus increase in response to noxious stimuli, and thus D2 receptor-mediated suppression of voltage-gated Ca2+ channels may be a novel neuroprotective mechanism for ORNs.
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Sunahara, Roger K., Philip Seeman, Hubert H. M. Van Tol, and Hyman B. Niznik. "Dopamine Receptors and Antipsychotic Drug Response." British Journal of Psychiatry 163, S22 (December 1993): 31–38. http://dx.doi.org/10.1192/s000712500029257x.
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Dopamine receptors have been divided into two major types – D1 and D2 – based primarily on pharmacological and biochemical criteria. Recent advances in the molecular biology of the dopamine receptor system have allowed the identification and characterisation of at least five distinct neuronal dopamine receptor genes (D1 to D5). These genes encode dopamine receptors belonging to the D1 receptor family, termed D1 and D5, and three D2-like receptors, termed D2, D3 and D4. These receptors are distinguished on the basis of their primary structure, chromosomal location, mRNA size and tissue distribution, and biochemical and pharmacological differences. Although individually these receptor subtypes may not be directly and exclusively involved in the maintenance or expression of schizophrenia, alterations of any of the receptors may contribute to the perturbation or instability of dopaminergic homeostasis in the brain. What was once thought to be a simple two-receptor system seems to have emerged as an intricate and interactive entity. This review summarises what is currently understood about dopamine receptors, their role in antipsychotic drug action, and their association with psychosis.
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Yang, Zhiwei, Laureano D. Asico, Peiying Yu, Zheng Wang, John E. Jones, Ren-kui Bai, David R. Sibley, Robin A. Felder, and Pedro A. Jose. "D5 dopamine receptor regulation of phospholipase D." American Journal of Physiology-Heart and Circulatory Physiology 288, no. 1 (January 2005): H55—H61. http://dx.doi.org/10.1152/ajpheart.00627.2004.
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D1-like receptors have been reported to decrease oxidative stress in vascular smooth muscle cells by decreasing phospholipase D (PLD) activity. However, the PLD isoform regulated by D1-like receptors (D1 or D5) and whether abnormal regulation of PLD by D1-like receptors plays a role in the pathogenesis of hypertension are unknown. The hypothesis that the D5 receptor is the D1-like receptor that inhibits PLD activity and serves to regulate blood pressure was tested using D5 receptor mutant mice (D5−/−). We found that in the mouse kidney, PLD2, like the D5 receptor, is mainly expressed in renal brush-border membranes, whereas PLD1 is mainly expressed in renal vessels with faint staining in brush-border membranes and collecting ducts. Total renal PLD activity is increased in D5−/− mice relative to congenic D5 wild-type (D5+/+) mice. PLD2, but not PLD1, expression is greater in D5−/− than in D5+/+ mice. The D5 receptor agonist fenoldopam decreases PLD2, but not PLD1, expression and activity in human embryonic kidney-293 cells heterologously expressing the human D5 receptor, effects that are blocked by the D5 receptor antagonist SCH-23390. These studies show that the D5 receptor regulates PLD2 activity and expression. The hypertension in the D5−/− mice is associated with increased PLD expression and activity. Impaired D5 receptor regulation of PLD2 may play a role in the pathogenesis of hypertension.
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Morra, M., F. Leboulenger, and H. Vaudry. "Characterization of dopamine receptors associated with steroid secretion in frog adrenocortical cells." Journal of Molecular Endocrinology 8, no. 1 (February 1992): 43–52. http://dx.doi.org/10.1677/jme.0.0080043.
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ABSTRACT We investigated the type of receptors involved in the mechanism of action of dopamine on corticosteroid secretion from the frog interrenal (adrenal) gland, using the in-vitro perifusion technique. Exposure of dispersed interrenal cells to 50 μm dopamine for 20 min had a biphasic effect on corticosterone and aldosterone secretion, i.e. a transient stimulation followed by an inhibitory phase. Repeated administration of equimolar pulses of dopamine, given at 150-min intervals, resulted in an enhancement of corticosteroid secretion followed by a subsequent blockade of the stimulatory phase of the response. In contrast, the dopamine-evoked inhibition of corticosteroid release did not show any sensitization or desensitization phenomena. Infusion of repeated pulses of the D1 receptor agonist SKF38393 (32 μm) stimulated corticosteroid release and mimicked the sensitization-desensitization phenomenon induced by dopamine. Repeated administration of the D2 receptor agonist LY171555 (50μm) resulted in a reproducible inhibition of corticosterone and aldosterone secretion. These results suggested the presence of two different receptors for dopamine, i.e. D1 and D2, on frog adrenocortical cells, responsible respectively for the stimulatory and inhibitory effects of dopamine on steroid secretion. However, bromocriptine (50 μm) and CV205-502 (50 μm), two other D2 receptor agonists, had no effect on corticosteroid release. In addition, several classical D2 receptor antagonists failed to block the effect of dopamine on steroidogenesis. It was also observed that (−)sulpiride, a specific D2 antagonist, did not alter dopamine-induced inhibition of inositol phosphate formation. On the other hand, dopamine and the selective D1 and D2 agonists SKF38393 and LY171555 did not affect the formation of cyclic AMP by interrenal tissue. Taken together, these data indicate that dopamine directly regulates corticosteroid secretion from frog adrenocortical cells. The effect of dopamine is not coupled to adenylate cyclase activity but is probably mediated through the phosphoinositide-turnover pathway. The pharmacological characteristics of the receptors involved in the mechanism of action of dopamine clearly differ from those of the D1 and D2 subtypes previously described in mammals.
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Cui, Qiaoling, Qian Li, Hongyan Geng, Lei Chen, Nancy Y. Ip, Ya Ke, and Wing-Ho Yung. "Dopamine receptors mediate strategy abandoning via modulation of a specific prelimbic cortex–nucleus accumbens pathway in mice." Proceedings of the National Academy of Sciences 115, no. 21 (May 7, 2018): E4890—E4899. http://dx.doi.org/10.1073/pnas.1717106115.
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The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex–nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task. This ability is dependent on an intact dopaminergic tone in the NAc, as local dopamine denervation impaired the performance of the animal in the switching of tasks. In addition, based on a brain-slice preparation obtained from Drd2-EGFP BAC transgenic mice, we demonstrated direct innervation of D2 receptor-expressing medium spiny neurons (D2-MSNs) in the NAc by prelimbic cortical neurons, which is under the regulation by presynaptic dopamine receptors. While presynaptic D1-type receptor activation enhances the glutamatergic transmission from the prelimbic cortex to D2-MSNs, D2-type receptor activation suppresses this synaptic connection. Furthermore, manipulation of this pathway by optogenetic activation or administration of a D1-type agonist or a D2-type antagonist could restore impaired task-switching flexibility in mice with local NAc dopamine depletion; this restoration is consistent with the effects of knocking down the expression of specific dopamine receptors in the pathway. Our results point to a critical role of a specific prelimbic cortex–NAc subpathway in mediating strategy abandoning, allowing the switching from one strategy to another in problem solving.
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Frankowska, Małgorzata, Joanna Miszkiel, Lucyna Pomierny-Chamioło, Bartosz Pomierny, Giuseppe Giannotti, Agata Suder, and Małgorzata Filip. "Alternation in dopamine D2-like and metabotropic glutamate type 5 receptor density caused by differing housing conditions during abstinence from cocaine self-administration in rats." Journal of Psychopharmacology 33, no. 3 (January 15, 2019): 372–82. http://dx.doi.org/10.1177/0269881118821113.
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Background: Environmental conditions have an important function in substance use disorder, increasing or decreasing the risks of relapse. Several studies strongly support the role of the dopamine D2-like and metabotropic glutamate type 5 receptors in maladaptive neurobiological responses to cocaine reward and relapse. Aims: The present study employed cocaine self-administration with yoked-triad procedure in rats to explore whether drug abstinence in different housing conditions affects the drug-seeking behaviour and the dopamine D2-like and metabotropic glutamate type 5 receptor density and affinity in several regions of the animal brain. Methods: Rats were trained to self-administer cocaine and later they were forced to abstain either in: (a) enriched environment or (b) isolation cage conditions to evaluate the effect of housing conditions on the drug-seeking behaviour and to assess changes concerning receptors in animals brain. Results: Our results show that exposure to enriched environment conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated a significant increase in the dopamine D2-like receptor density in the prefrontal cortex in animals following drug abstinence in isolation cage or enriched environment conditions, and the reduction in their density in the dorsal striatum provoked by isolation cage conditions. The metabotropic glutamate type 5 receptor density decreased only in the prefrontal cortex after isolation cage and enriched environment abstinence. Conclusions: This study shows the different impacts caused by the type of housing conditions during abstinence from cocaine self-administration on drug-seeking behaviour in rats. The observed changes in the dopamine D2-like and metabotropic glutamate type 5 receptor Bmax and/or Kd values were brain-region specific and related to either pharmacological and/or motivational features of cocaine.
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Kovtun, Oleg, Ruben Torres, Laurel G. Bellocchio, and Sandra Jean Rosenthal. "Membrane Nanoscopic Organization of D2L Dopamine Receptor Probed by Quantum Dot Tracking." Membranes 11, no. 8 (July 30, 2021): 578. http://dx.doi.org/10.3390/membranes11080578.
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The role of lateral mobility and nanodomain organization of G protein-coupled receptors in modulating subcellular signaling has been under increasing scrutiny. Investigation of D2 dopamine receptor diffusion dynamics is of particular interest, as these receptors have been linked to altered neurotransmission in affective disorders and represent the primary target for commonly prescribed antipsychotics. Here, we applied our single quantum dot tracking approach to decipher intrinsic diffusion patterns of the wild-type long isoform of the D2 dopamine receptor and its genetic variants previously identified in several cohorts of schizophrenia patients. We identified a subtle decrease in the diffusion rate of the Val96Ala mutant that parallels its previously reported reduced affinity for potent neuroleptics clozapine and chlorpromazine. Slower Val96Ala variant diffusion was not accompanied by a change in receptor-receptor transient interactions as defined by the diffraction-limited quantum dot colocalization events. In addition, we implemented a Voronoї tessellation-based algorithm to compare nanoclustering of the D2 dopamine receptor to the dominant anionic phospholipid phosphatidylinositol 4,5-bisphosphate in the plasma membrane of live cells.
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Brunig, I., M. Sommer, H. Hatt, and J. Bormann. "Dopamine receptor subtypes modulate olfactory bulb -aminobutyric acid type A receptors." Proceedings of the National Academy of Sciences 96, no. 5 (March 2, 1999): 2456–60. http://dx.doi.org/10.1073/pnas.96.5.2456.
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Davila, Nestor G., Laura J. Blakemore, and Paul Q. Trombley. "Dopamine Modulates Synaptic Transmission Between Rat Olfactory Bulb Neurons in Culture." Journal of Neurophysiology 90, no. 1 (July 2003): 395–404. http://dx.doi.org/10.1152/jn.01058.2002.
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The glomerular layer of the olfactory bulb (OB) contains synaptic connections between olfactory sensory neurons and OB neurons as well as connections among OB neurons. A subpopulation of external tufted cells and periglomerular cells (juxtaglomerular neurons) expresses dopamine, and recent reports suggest that dopamine can inhibit olfactory sensory neuron activation of OB neurons. In this study, whole cell electrophysiological and primary culture techniques were employed to characterize the neuromodulatory properties of dopamine on glutamatergic transmission between rat OB mitral/tufted (M/T) cells and interneurons. Immunocytochemical analysis confirmed the expression of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, in a subpopulation of cultured neurons. D2 receptor immunoreactivity was also observed in cultured M/T cells. Dopamine reduced spontaneous excitatory synaptic events recorded in interneurons. Although the D1 receptor agonist SKF38393 and the D2 receptor agonist bromocriptine mesylate mimicked this effect, evoked excitatory postsynaptic potentials (EPSPs) recorded from monosynaptically coupled neuron pairs were attenuated by dopamine and bromocriptine but not by SKF38393 . Neither glutamate-evoked currents nor the membrane resistance of the postsynaptic interneuron were affected by dopamine. However, evoked calcium channel currents in the presynaptic M/T cell were diminished during the application of either dopamine or bromocriptine, but not SKF38393 . Dopamine suppressed calcium channel currents even after nifedipine blockade of L-type channels, suggesting that inhibition of the dihydropyridine-resistant high-voltage activated calcium channels implicated in transmitter release may mediate dopamine's effects on spontaneous and evoked synaptic transmission. Together, these data suggest that dopamine inhibits excitatory neurotransmission between M/T cells and interneurons via a presynaptic mechanism.
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Zheng, Hong, Xuefei Liu, Yulong Li, Paras K. Mishra, and Kaushik P. Patel. "Attenuated dopaminergic tone in the paraventricular nucleus contributing to sympathoexcitation in rats with Type 2 diabetes." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 306, no. 2 (January 15, 2014): R138—R148. http://dx.doi.org/10.1152/ajpregu.00323.2013.
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The study was conducted to investigate the role for dopamine in the centrally mediated sympathoexcitatory response in rats with Type 2 diabetes (T2D). T2D was induced by a combination of high-fat diet (HFD) and low-dose streptozotocin (STZ). HFD/STZ treatment for 12–14 wk resulted in significant increase in the number of FosB-positive cells in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM). In anesthetized rats, administration of exogenous dopamine (dopamine hydrochloride, 20 mM) in the PVN, but not in the RVLM, elicited decreases in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in control rats and but not in the T2D rats. Blocking the endogenous dopamine with dopamine D1/D5 receptor antagonist SCH39166 (2 mM) in the PVN and RVLM, resulted in increases in RSNA, MAP, and heart rate (HR) in both control and T2D rats. These responses were significantly attenuated in T2D rats compared with control rats (PVN − ΔRSNA: 21 ± 10 vs. 44 ± 2%; ΔMAP: 7 ± 3 vs. 19 ± 6 mmHg, ΔHR: 17 ± 5 vs. 32 ± 4 bpm, P < 0.05). There were no significant increases in response to dopamine D2/D3 receptor antagonist raclopride application in the PVN and RVLM of both control and T2D rats. Furthermore, there were decreased dopamine D1 receptor and D2 receptor expressions in the PVN of T2D rats. Taken together, these data suggest that reduced endogenous dopaminergic tone within the PVN may contribute to the sympathoexcitation in T2D.
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Carroll, J. L., K. M. Boyle, M. J. Wasicko, and L. M. Sterni. "Dopamine D2 receptor modulation of carotid body type 1 cell intracellular calcium in developing rats." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 5 (May 2005): L910—L916. http://dx.doi.org/10.1152/ajplung.00414.2003.
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Carotid chemoreceptor type 1 cells release dopamine, which inhibits carotid chemoreceptor activity via dopamine D2 autoreceptors on type 1 cells. Postnatal changes in dopaminergic modulation may be involved in postnatal chemoreceptor development. The present study explores dopaminergic modulation of the intracellular calcium ([Ca2+]i) response to hypoxia in type 1 cells from 1, 3, and 11- to 16-day-old rats. Using fura-2, we studied the effects of quinpirole, a D2 receptor agonist, on type 1 cell [Ca2+]i response to 90-s hypoxia challenges (Po2 ∼1–2 mmHg). Cells were sequentially exposed to the following challenges: 1) hypoxia control, 2) hypoxia plus quinpirole, and 3) hypoxia plus quinpirole plus sulpiride (D2 receptor antagonist). In the 11- to 16-day-old group, type 1 cell [Ca2+]i increased ∼3 to 4-fold over resting [Ca2+]i in response to hypoxia. Quinpirole (10 μM) significantly blunted the peak [Ca2+]i response to hypoxia. Repeat challenge with hypoxia plus 10 μM quinpirole in the presence of 10 μM sulpiride partially restored the hypoxia [Ca2+]i response. In sharp contrast to the older aged group, 10 μM quinpirole had minimal effect on hypoxia response of type 1 cells from 1-day-olds and a small but significant effect at 3 days of age. We conclude that stimulation of dopamine D2 receptors inhibits type 1 cell [Ca2+]i response to hypoxia, consistent with an inhibitory autoreceptor role. These findings suggest dopamine-mediated inhibition and oxygen sensitivity increase with age on a similar time course and do not support a role for dopamine as a major mediator of carotid chemoreceptor resetting.
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Shultz, P. J., J. R. Sedor, and H. E. Abboud. "Dopaminergic stimulation of cAMP accumulation in cultured rat mesangial cells." American Journal of Physiology-Heart and Circulatory Physiology 253, no. 2 (August 1, 1987): H358—H364. http://dx.doi.org/10.1152/ajpheart.1987.253.2.h358.
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Dopamine (DA) alters renal hemodynamics, and DA receptors have been demonstrated in isolated glomeruli. To determine the glomerular cell type bearing DA receptors, we studied the effect of dopaminergic agonists and antagonists on adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat glomerular mesangial and epithelial cells in culture. DA caused a marked dose- and time-dependent increase in cAMP accumulation in mesangial but not epithelial cells. The stimulatory effect of DA was abolished by the DA antagonists haloperidol, trifluoperazine, and cis-thiothixene but not by beta- or alpha-adrenergic or histamine antagonists. Similar to the effects of DA, two dopamine type I receptor agonists, fenoldopam and SKF 38393, markedly stimulated cAMP accumulation in the mesangial cells. Moreover, the effects of DA were blocked by Sch 23390, a specific DA1 receptor antagonist, but not domperidone, a specific DA2 antagonist. These results show that DA regulates cAMP accumulation in mesangial cells via DA1-type receptors.
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Günther, Thomas, Michael Culler, and Stefan Schulz. "Research Resource: Real-Time Analysis of Somatostatin and Dopamine Receptor Signaling in Pituitary Cells Using a Fluorescence-Based Membrane Potential Assay." Molecular Endocrinology 30, no. 4 (April 1, 2016): 479–90. http://dx.doi.org/10.1210/me.2015-1241.
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Stable somatostatin analogues and dopamine receptor agonists are the mainstay for the pharmacological treatment of functional pituitary adenomas; however, only a few cellular assays have been developed to detect receptor activation of novel compounds without disrupting cells to obtain the second messenger content. Here, we adapted a novel fluorescence-based membrane potential assay to characterize receptor signaling in a time-dependent manner. This minimally invasive technique provides a robust and reliable read-out for ligand-induced receptor activation in permanent and primary pituitary cells. The mouse corticotropic cell line AtT-20 endogenously expresses both the somatostatin receptors 2 (sst2) and 5 (sst5). Exposure of wild-type AtT-20 cells to the sst2- and sst5-selective agonists BIM-23120 and BIM-23268, respectively, promoted a pertussis toxin- and tertiapin-Q-sensitive reduction in fluorescent signal intensity, which is indicative of activation of G protein-coupled inwardly rectifying potassium (GIRK) channels. After heterologous expression, sst1, sst3, and sst4 receptors also coupled to GIRK channels in AtT-20 cells. Similar activation of GIRK channels by dopamine required overexpression of dopamine D2 receptors (D2Rs). Interestingly, the presence of D2Rs in AtT-20 cells strongly facilitated GIRK channel activation elicited by the sst2-D2 chimeric ligand BIM-23A760, suggesting a synergistic action of sst2 and D2Rs. Furthermore, stable somatostatin analogues produced strong responses in primary pituitary cultures from wild-type mice; however, in cultures from sst2 receptor-deficient mice, only pasireotide and somatoprim, but not octreotide, induced a reduction in fluorescent signal intensity, suggesting that octreotide mediates its pharmacological action primarily via the sst2 receptor.
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Thornberg, Sheri A., and Larry Ereshefsky. "Neuroleptic Malignant Syndrome Associated With Clozapine Monotherapy." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 13, no. 5 (September 10, 1993): 510–14. http://dx.doi.org/10.1002/j.1875-9114.1993.tb04317.x.
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Neuroleptic malignant syndrome is thought to be a result of dopamine receptor blockade in the striatum. Clozapine has only weak affinity for dopamine type 1 and 2 receptors, and therefore it was thought this drug would not precipitate the syndrome. However, six cases of the syndrome have been reported in patients receiving clozapine monotherapy. A review of the pathoetiology of symptoms occurring in the syndrome is included.
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Enzensperger, Christoph, and Jochen Lehmann. "Dopamine/Serotonin Receptor Ligands. 131: Homologization of a Benzindoloazecine-Type Dopamine Receptor Antagonist Modulates the Affinities for Dopamine D1−D5Receptors." Journal of Medicinal Chemistry 49, no. 21 (October 2006): 6408–11. http://dx.doi.org/10.1021/jm060213k.
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Čikoš, Štefan, Dušan Fabian, Ján Burkuš, Žofia Janštová, and Juraj Koppel. "Expression of dopamine and adrenergic receptors in mouse embryonic stem cells and preimplantation embryos." Biologia 70, no. 9 (September 1, 2015): 1263–71. http://dx.doi.org/10.1515/biolog-2015-0141.
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Abstract Using RT-PCR we examined expression of dopamine and adrenergic receptors in undifferentiated and spontaneously differentiating mouse embryonic stem (ES) cells. We also examined expression of dopamine receptor subtypes in mouse ovulated oocytes and preimplantation embryos. Comparing the expression of catecholamine receptors in undifferentiated mouse ES cells and in blastocysts (from which ES cells are derived), we found that transcripts of all five dopamine receptors were expressed in both cell types. In contrast, we detected eight adrenergic receptor subtypes in undifferentiated mouse ES cells, but only three subtypes were found in mouse blastocysts. In three adrenergic receptors (α1D, α2B, β1), we found higher expression in the spontaneously differentiating ES cells than in undifferentiated ES cells, and the α1B adrenoceptor was not even detectable in the undifferentiated cells. These results indicate that genes encoding all types of catecholamine receptors are transcribed in mouse ES cells, and some of them are differentially expressed during ES cell differentiation. We found several profiles of dopamine receptor mRNA expression during the preimplantation period. The DR3 transcript was present in all examined stages (oocytes, 4-cell embryos, 8- to 16-cell embryos, blastocysts). DR1 and DR4 transcripts were not found in oocytes, but we detected them in preimplantation embryos. The DR2 receptor transcript was found in all examined stages except for the 4-cell embryos, and the DR5 receptor transcript was found in all examined stages except for the 8- to 16-cell embryos. The expression profiles of dopamine receptor transcripts suggest different roles of some receptor subtypes in particular preimplantation developmental stages.
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Kandasamy, Krishnaveni, Abinaya Paramanandham, Goshika Russel Suthi Kumari, and Kameswaran Ramalingam. "A comprehensive review on the role of dopamine in the pathophysiology of tardive dyskinesia." International Journal of Research in Medical Sciences 11, no. 10 (September 29, 2023): 3925–30. http://dx.doi.org/10.18203/2320-6012.ijrms20233065.
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Tardive dyskinesia (TD) is a neurological syndrome characterized by involuntary, repetitive, and unusual movements that primarily impact the orofacial region while also extending to other body parts, encompassing chorea, dystonia, tics, buccolingual stereotypy, and akathisia. This condition stems from iatrogenic factors, particularly the chronic administration of medications that obstruct dopamine receptors. Predominantly implicated are antipsychotic drugs, utilized primarily for schizophrenia and bipolar disorder treatment. These drugs modulate dopamine levels, yet prolonged usage can induce alterations in dopamine receptor sensitivity and disruptions in dopaminergic pathways, consequently fostering TD. Dopamine, a pivotal neurotransmitter governing motor control, motivation, reward processing, and emotional regulation, exerts its effects through distinct dopamine receptor types, of which the D2 subtype assumes particular significance in TD development. The persistent blockade of D2 receptors by antipsychotics prompts a compensatory surge in receptor numbers and sensitivity, ultimately contributing to TD's emergence. In essence, TD reflects a complex interplay between medical intervention and neurological intricacies. The protracted influence of antipsychotics on dopamine receptors highlights the delicate equilibrium essential for optimal brain function. The unconventional movements characterizing TD underscore the intricate role of dopamine and its receptors in orchestrating neural equilibrium.
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Umemiya, Masashi, and Lynn A. Raymond. "Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons." Journal of Neurophysiology 78, no. 3 (September 1, 1997): 1248–55. http://dx.doi.org/10.1152/jn.1997.78.3.1248.
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Umemiya, Masashi and Lynn A. Raymond. Dopaminergic modulation of excitatory postsynaptic currents in rat neostriatal neurons. J. Neurophysiol. 78: 1248–1255, 1997. γ-aminobutyric acid (GABA)-containing medium spiny neurons constitute ∼90% of the neuronal population in the neostriatum (caudate and putamen) and play an important role in motor programming. Cortical glutamatergic afferents provide the main excitatory drive for these neurons, whereas nigral dopaminergic neurons play a crucial role in regulating their activity. To further investigate the mechanisms underlying the dopaminergic modulation of medium spiny neuronal activity, we tested the effect of dopamine receptor agonists on excitatory synaptic transmission recorded from these neurons. Excitatory postsynaptic currents (EPSCs) were evoked by local stimulation and recorded from medium spiny neurons in postnatal rat striatal thin brain slices. Recordings were made using the whole cell patch-clamp technique under voltage clamp and conditions that selected for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate- and kainate-type glutamate receptor-mediated components of the EPSC. Incubation of slices in 10 μM dopamine resulted in a 33 ± 11% (mean ± SE) decrease in the amplitude of evoked EPSCs, an effect that developed during seconds. The relative variability in amplitude of dopamine's effects on medium spiny neuron EPSCs may reflect activation of different receptor subtypes with opposing effects. In contrast to the results with dopamine, incubation of slices in SKF 38393, a D1-type dopamine receptor selective agonist, resulted in dose-dependent potentiation of the medium spiny neuron EPSC that developed during several minutes. At a concentration of 5 μM, SKF 38393 resulted in a 29 ± 4.5% increase in EPSC amplitude, an effect that was blocked by preincubation with the D1-selective antagonist, SCH 23390 (10 μM). On the other hand, 5 μM SKF 38393 had no apparent effect on medium spiny neuron currents activated by exogenous application of glutamate or kainate. However, because of the inherent limitations of rapid agonist perfusion in the brain slice preparation (caused by slow agonist diffusion and rapid glutamate receptor desensitization) and because of anatomic evidence that colocalizes D1 and glutamate receptors to medium spiny neuron dendrites, our results leave open the possibility that the effect of D1 receptor activation on the EPSC is mediated via modulation of postsynaptic glutamate receptor responsiveness. The significant potentiation by D1 receptor agonists of EPSC amplitude at the cortico-striatal medium spiny synapse that we observed, in part, may underlie the role of D1 receptors in facilitating medium spiny neuronal firing, with implications for understanding regulation of movement.
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Marwaha, Aditi, Anees Ahmad Banday, and Mustafa F. Lokhandwala. "Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats." American Journal of Physiology-Renal Physiology 286, no. 3 (March 2004): F451—F457. http://dx.doi.org/10.1152/ajprenal.00227.2003.
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Dopamine, via activation of renal D1 receptors, inhibits the activities of Na-K-ATPase and Na/H exchanger and subsequently increases sodium excretion. Decreased renal dopamine production and sodium excretion are associated with type I diabetes. However, it is not known whether the response to D1 receptor activation is altered in type I diabetes. The present study was designed to examine the effect of streptozotocin-induced type I diabetes on renal D1 receptor expression and function. Streptozotocin treatment of Sprague-Dawley rats caused a fourfold increase in plasma levels of glucose along with a significant decrease in insulin levels compared with control rats. Intravenous administration of SKF-38393, a D1 receptor agonist, caused a threefold increase in sodium excretion in control rats. However, SKF-38393 failed to produce natriuresis in diabetic rats. SKF-38393 caused a concentration-dependent inhibition of Na-K-ATPase activity in renal proximal tubules of control rats. However, the ability of SKF-38393 to inhibit Na-K-ATPase activity was markedly diminished in diabetic rats. D1 receptor numbers and protein abundance as determined by [3H]SCH-23390 ligand binding and Western blot analysis were markedly reduced in diabetic rats compared with control rats. Moreover, SKF-38393 failed to stimulate GTPγS binding in proximal tubular membranes from diabetic rats compared with control rats. We conclude that the natriuretic response to D1 receptor activation is reduced in type I diabetes as a result of a decrease in D1 receptor expression and defective receptor G protein coupling. These abnormalities may contribute to the sodium retention associated with type I diabetes.
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Bhagwanth, Swapna, Ram K. Mishra, and Rodney L. Johnson. "Development of peptidomimetic ligands of Pro-Leu-Gly-NH2 as allosteric modulators of the dopamine D2 receptor." Beilstein Journal of Organic Chemistry 9 (January 30, 2013): 204–14. http://dx.doi.org/10.3762/bjoc.9.24.
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A variety of stable, small-molecule peptidomimetic ligands have been developed to elucidate the mechanism by which the neuropeptide Pro-Leu-Gly-NH2 (PLG) modulates dopaminergic neurotransmission. Photoaffinity labeling ligands based upon PLG peptidomimetics have been used to establish that PLG binds to the D2 dopamine receptor at a site that is different from the orthosteric site, thus making PLG and its peptidomimetics allosteric modulators of the dopamine receptor. Through the design, synthesis and pharmacological evaluation of conformationally constrained peptidomimetics containing lactam, bicyclic, and spiro-bicyclic scaffolds, support was provided for the hypothesis that the bioactive conformation of PLG is a type II β-turn. In addition, studies with peptidomimetics designed to mimic either a type VI β-turn or polyproline II helix conformation yielded molecules that were able to modulate dopamine receptors because of their ability to place the carboxamide NH2 pharmacophore in the same topological space as that seen in the type II β-turn. Extensive studies with the spiro-bicyclic PLG peptidomimetics also established that both positive and negative modes of modulation were possible for the same series of peptidomimetics simply as a result of minor differences in the stereochemistry about the bridgehead carbon within the scaffold. This information was used to transform existing positive modulators into negative modulators, which demonstrated that small structural changes in the spiro-bicyclic dopamine receptor modulators are capable of causing major changes in the modulatory activity of PLG peptidomimetics.
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Kawahata, Ichiro, Tomoki Sekimori, Haoyang Wang, Yanyan Wang, Toshikuni Sasaoka, Luc Bousset, Ronald Melki, Tomohiro Mizobata, Yasushi Kawata, and Kohji Fukunaga. "Dopamine D2 Long Receptors Are Critical for Caveolae-Mediated α-Synuclein Uptake in Cultured Dopaminergic Neurons." Biomedicines 9, no. 1 (January 8, 2021): 49. http://dx.doi.org/10.3390/biomedicines9010049.
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α-synuclein accumulation into dopaminergic neurons is a pathological hallmark of Parkinson’s disease. We previously demonstrated that fatty acid-binding protein 3 (FABP3) is critical for α-synuclein uptake and propagation to accumulate in dopaminergic neurons. FABP3 is abundant in dopaminergic neurons and interacts with dopamine D2 receptors, specifically the long type (D2L). Here, we investigated the importance of dopamine D2L receptors in the uptake of α-synuclein monomers and their fibrils. We employed mesencephalic neurons derived from dopamine D2L−/−, dopamine D2 receptor null (D2 null), FABP3−/−, and wild type C57BL6 mice, and analyzed the uptake ability of fluorescence-conjugated α-synuclein monomers and fibrils. We found that D2L receptors are co-localized with FABP3. Immunocytochemistry revealed that TH+ D2L−/− or D2 null neurons do not take up α-synuclein monomers. The deletion of α-synuclein C-terminus completely abolished the uptake to dopamine neurons. Likewise, dynasore, a dynamin inhibitor, and caveolin-1 knockdown also abolished the uptake. D2L and FABP3 were also critical for α-synuclein fibrils uptake. D2L and accumulated α-synuclein fibrils were well co-localized. These data indicate that dopamine D2L with a caveola structure coupled with FABP3 is critical for α-synuclein uptake by dopaminergic neurons, suggesting a novel pathogenic mechanism of synucleinopathies, including Parkinson’s disease.
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Kawahata, Ichiro, Tomoki Sekimori, Haoyang Wang, Yanyan Wang, Toshikuni Sasaoka, Luc Bousset, Ronald Melki, Tomohiro Mizobata, Yasushi Kawata, and Kohji Fukunaga. "Dopamine D2 Long Receptors Are Critical for Caveolae-Mediated α-Synuclein Uptake in Cultured Dopaminergic Neurons." Biomedicines 9, no. 1 (January 8, 2021): 49. http://dx.doi.org/10.3390/biomedicines9010049.
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α-synuclein accumulation into dopaminergic neurons is a pathological hallmark of Parkinson’s disease. We previously demonstrated that fatty acid-binding protein 3 (FABP3) is critical for α-synuclein uptake and propagation to accumulate in dopaminergic neurons. FABP3 is abundant in dopaminergic neurons and interacts with dopamine D2 receptors, specifically the long type (D2L). Here, we investigated the importance of dopamine D2L receptors in the uptake of α-synuclein monomers and their fibrils. We employed mesencephalic neurons derived from dopamine D2L−/−, dopamine D2 receptor null (D2 null), FABP3−/−, and wild type C57BL6 mice, and analyzed the uptake ability of fluorescence-conjugated α-synuclein monomers and fibrils. We found that D2L receptors are co-localized with FABP3. Immunocytochemistry revealed that TH+ D2L−/− or D2 null neurons do not take up α-synuclein monomers. The deletion of α-synuclein C-terminus completely abolished the uptake to dopamine neurons. Likewise, dynasore, a dynamin inhibitor, and caveolin-1 knockdown also abolished the uptake. D2L and FABP3 were also critical for α-synuclein fibrils uptake. D2L and accumulated α-synuclein fibrils were well co-localized. These data indicate that dopamine D2L with a caveola structure coupled with FABP3 is critical for α-synuclein uptake by dopaminergic neurons, suggesting a novel pathogenic mechanism of synucleinopathies, including Parkinson’s disease.
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Robaa, Dina, Christoph Enzensperger, Shams El Din Abul Azm, El Sayeda El Khawass, Ola El Sayed, and Jochen Lehmann. "Dopamine Receptor Ligands. Part 18:(1) Modification of the Structural Skeleton of Indolobenzazecine-Type Dopamine Receptor Antagonists." Journal of Medicinal Chemistry 53, no. 6 (March 25, 2010): 2646–50. http://dx.doi.org/10.1021/jm901291r.
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Sung, Yun-Min, Angela D. Wilkins, Gustavo J. Rodriguez, Theodore G. Wensel, and Olivier Lichtarge. "Intramolecular allosteric communication in dopamine D2 receptor revealed by evolutionary amino acid covariation." Proceedings of the National Academy of Sciences 113, no. 13 (March 15, 2016): 3539–44. http://dx.doi.org/10.1073/pnas.1516579113.
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The structural basis of allosteric signaling in G protein-coupled receptors (GPCRs) is important in guiding design of therapeutics and understanding phenotypic consequences of genetic variation. The Evolutionary Trace (ET) algorithm previously proved effective in redesigning receptors to mimic the ligand specificities of functionally distinct homologs. We now expand ET to consider mutual information, with validation in GPCR structure and dopamine D2 receptor (D2R) function. The new algorithm, called ET-MIp, identifies evolutionarily relevant patterns of amino acid covariations. The improved predictions of structural proximity and D2R mutagenesis demonstrate that ET-MIp predicts functional interactions between residue pairs, particularly potency and efficacy of activation by dopamine. Remarkably, although most of the residue pairs chosen for mutagenesis are neither in the binding pocket nor in contact with each other, many exhibited functional interactions, implying at-a-distance coupling. The functional interaction between the coupled pairs correlated best with the evolutionary coupling potential derived from dopamine receptor sequences rather than with broader sets of GPCR sequences. These data suggest that the allosteric communication responsible for dopamine responses is resolved by ET-MIp and best discerned within a short evolutionary distance. Most double mutants restored dopamine response to wild-type levels, also suggesting that tight regulation of the response to dopamine drove the coevolution and intramolecular communications between coupled residues. Our approach provides a general tool to identify evolutionary covariation patterns in small sets of close sequence homologs and to translate them into functional linkages between residues.
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Ferone, Diego, Federico Gatto, Marica Arvigo, Eugenia Resmini, Mara Boschetti, Claudia Teti, Daniela Esposito, and Francesco Minuto. "The clinical–molecular interface of somatostatin, dopamine and their receptors in pituitary pathophysiology." Journal of Molecular Endocrinology 42, no. 5 (January 13, 2009): 361–70. http://dx.doi.org/10.1677/jme-08-0162.
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The role of somatostatin and dopamine receptors as molecular targets for the treatment of patients with pituitary adenomas is well established. Indeed, dopamine and somatostatin receptor agonists are considered milestones for the medical therapy of these tumours. However, in recent years, the knowledge of the expression of subtypes of somatostatin and dopamine receptors in pituitary adenomas, as well as of the coexpression of both types of receptors in tumour cells, has increased considerably. Moreover, recent insights suggest a functional interface of dopamine and somatostatin receptors, when coexpressed in the same cells. This interaction has been suggested to occur via dimerisation of these G-protein-coupled receptors. In addition, there was renewed interest around the concept of cell specificity in response to ligand-induced receptor activation. New experimental drugs, including novel somatostatin analogues, binding to multiple somatostatin receptor subtypes, as well as hybrid somatostatin–dopamine compounds have been generated, and recently a completely novel class of molecules has been developed. These advances have opened new perspectives for the medical treatment of patients with pituitary tumours poorly responsive to the present clinically available drugs, and perhaps also for the treatment of other categories of neuroendocrine tumours. The aim of the present review is to summarise the novel insights in somatostatin and dopamine receptor pathophysiology, and to bring these new insights into perspective for the future strategies in the medical treatment of patients with pituitary adenomas.
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Chen, X., and T. C. Westfall. "Modulation of intracellular calcium transients and dopamine release by neuropeptide Y in PC-12 cells." American Journal of Physiology-Cell Physiology 266, no. 3 (March 1, 1994): C784—C793. http://dx.doi.org/10.1152/ajpcell.1994.266.3.c784.
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In PC-12 cells differentiated with nerve growth factor, neuropeptide Y (NPY) potentiated the K(+)-evoked increase in intracellular calcium, but this potentiation was not mediated by classical Y1 or Y2 NPY receptors. The potentiation by NPY appeared to occur through the mobilization of calcium from intracellular stores because thapsigargin successfully blocked the potentiation. In contrast, the Y2 agonist, NPY-(13-36), attenuated the K(+)-evoked increase in intracellular calcium by decreasing the influx of extracellular calcium. The effect of NPY-(13-36) on dopamine release from PC-12 cells was next studied. NPY-(13-36) significantly attenuated the K(+)-evoked dopamine release in a concentration-dependent manner. Nifedipine and omega-conotoxin also attenuated the evoked dopamine release. In the presence of nifedipine or omega-conotoxin, NPY-(13-36) produced further inhibition of the evoked dopamine release. Furthermore, NPY-(13-36)-induced inhibition of dopamine release was abolished by pertussis toxin pretreatment. We conclude that the regulatory effects of NPY and analogues on intracellular calcium are mediated by multiple NPY receptor subtypes. Y2 receptor-mediated pertussis toxin-sensitive inhibition of the evoked dopamine release does not seem to be due to interactions with L- or N-type Ca2+ channels.
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Ennis, Riley Charles, Laureano D. Asico, Ines Armando, Jian Yang, Jun B. Feranil, Julie A. Jurgens, Crisanto S. Escano, et al. "Dopamine D1-like receptors regulate the α1A-adrenergic receptor in human renal proximal tubule cells and D1-like dopamine receptor knockout mice." American Journal of Physiology-Renal Physiology 307, no. 11 (December 1, 2014): F1238—F1248. http://dx.doi.org/10.1152/ajprenal.00119.2014.
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The homeostatic control of blood pressure hinges upon the delicate balance between prohypertensinogenic and antihypertensinogenic systems. D1-like dopamine receptors [dopamine D1 and D5 receptors (D1Rs and D5Rs, respectively)] and the α1A-adrenergic receptor (α1A-AR) are expressed in the renal proximal tubule and engender opposing effects on Na+ transport, i.e., natriuresis (via D1Rs and D5Rs) or antinatriuresis (via α1A-ARs). We tested the hypothesis that the D1R/D5R regulates the α1A-AR. D1-like dopamine receptors coimmunoprecipitated, colocalized, and cofractionated with α1A-ARs in lipid rafts in immortalized human renal proximal tubule cells. Long-term treatment with the D1R/D5R agonist fenoldopam resulted in decreased D1R and D5R expression but increased α1A-AR abundance in the plasma membrane. Short-term fenoldopam treatment stimulated the translocation of Na+-K+-ATPase from the plasma membrane to the cytosol that was partially reversed by an α1A-AR agonist, which by itself induced Na+-K+-ATPase translocation from the cytosol to the plasma membrane. The α1A-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na+-K+-ATPase activity. To determine the interaction among D1Rs, D5Rs, and α1A-ARs in vivo, we used phenylephrine and A610603 to decrease Na+ excretion in several D1-like dopamine receptor knockout mouse strains. Phenylephrine and A61603 treatment resulted in a partial reduction of urinary Na+ excretion in wild-type mice and its abolition in D1R knockout, D5R knockout, and D1R-D5R double-knockout mice. Our results demonstrate the ability of the D1-like dopamine receptors to regulate the expression and activity of α1A-AR. Elucidating the intricacies of the interaction among these receptors is crucial for a better understanding of the crosstalk between anti- and pro-hypertensive systems.
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Anastasiades, Paul G., Christina Boada, and Adam G. Carter. "Cell-Type-Specific D1 Dopamine Receptor Modulation of Projection Neurons and Interneurons in the Prefrontal Cortex." Cerebral Cortex 29, no. 7 (December 19, 2018): 3224–42. http://dx.doi.org/10.1093/cercor/bhy299.
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Abstract Dopamine modulation in the prefrontal cortex (PFC) mediates diverse effects on neuronal physiology and function, but the expression of dopamine receptors at subpopulations of projection neurons and interneurons remains unresolved. Here, we examine D1 receptor expression and modulation at specific cell types and layers in the mouse prelimbic PFC. We first show that D1 receptors are enriched in pyramidal cells in both layers 5 and 6, and that these cells project to intratelencephalic targets including contralateral cortex, striatum, and claustrum rather than to extratelencephalic structures. We then find that D1 receptors are also present in interneurons and enriched in superficial layer VIP-positive (VIP+) interneurons that coexpresses calretinin but absent from parvalbumin-positive (PV+) and somatostatin-positive (SOM+) interneurons. Finally, we determine that D1 receptors strongly and selectively enhance action potential firing in only a subset of these corticocortical neurons and VIP+ interneurons. Our findings define several novel subpopulations of D1+ neurons, highlighting how modulation via D1 receptors can influence both excitatory and disinhibitory microcircuits in the PFC.
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Helms, My N., Julie Self, Hui Fang Bao, Lauren C. Job, Lucky Jain, and Douglas C. Eaton. "Dopamine activates amiloride-sensitive sodium channels in alveolar type I cells in lung slice preparations." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 4 (October 2006): L610—L618. http://dx.doi.org/10.1152/ajplung.00426.2005.
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Active Na+ reabsorption by alveolar epithelial cells generates the driving force used to clear fluids from the air space. Using single-channel methods, we examined epithelial Na+ channel (ENaC) activity of alveolar type I (AT1) cells from live 250- to 300-μm sections of lung tissue, circumventing concerns that protracted cell isolation procedures might compromise the innate transport properties of native lung cells. We used fluorescein-labeled Erythrina crystagalli lectin to positively identify AT1 cells for single-channel patch-clamp analysis. We demonstrated, for the first time, single-channel recordings of highly selective and nonselective amiloride-sensitive ENaC channels (HSC and NSC, respectively) from AT1 cells in situ, with mean conductances of 8.2 ± 2.5 and 22 ± 3.2 pS, respectively. Additionally, 25 nM amiloride in the patch electrode blocked Na+ channel activity in AT1 cells. Immunohistochemical studies demonstrated the presence of dopamine D1 and D2 receptors on the surface of AT1 cells, and single-channel recordings showed that 10 μM dopamine increased Na+ channel activity [product of the number of channels and single-channel open probability ( NPo)] from 0.31 ± 0.19 to 0.60 ± 0.21 ( P < 0.001). The D1 receptor antagonist SCH-23390 (10 μM) blocked the stimulatory effect of dopamine on AT1 cells, but the D2 receptor antagonist sulpiride did not.
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Broft, Allegra, Mark Slifstein, Joseph Osborne, Paresh Kothari, Simon Morim, Rebecca Shingleton, Lindsay Kenney, et al. "Striatal dopamine type 2 receptor availability in anorexia nervosa." Psychiatry Research: Neuroimaging 233, no. 3 (September 2015): 380–87. http://dx.doi.org/10.1016/j.pscychresns.2015.06.013.
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Recouvreux, M. Victoria, M. Clara Guida, Daniel B. Rifkin, Damasia Becu-Villalobos, and Graciela Díaz-Torga. "Active and Total Transforming Growth Factor-β1 Are Differentially Regulated by Dopamine and Estradiol in the Pituitary." Endocrinology 152, no. 7 (April 26, 2011): 2722–30. http://dx.doi.org/10.1210/en.2010-1464.
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Dopamine, acting through the dopamine type 2 receptor (Drd2), is the main inhibitor of pituitary prolactin (PRL) secretion and lactotroph proliferation. TGF-β1 is involved, at least in part, in mediating these actions. It was described that TGF-β1 synthesis in rat pituitary lactotrophs is up-regulated by dopamine and down-regulated by estradiol. TGF-β1 is secreted as a large latent complex. The local regulation of cytokine activation in the pituitary has not yet been explored. In this work, we studied pituitary active and total TGF-β1 content, as well as TGF-β1 mRNA, and the in vivo role of dopamine and estradiol on pituitary TGF-β1 levels. Adult female mice (wild type), and female mice with a null mutation in the Drd2 (Drd2−/−), were used. The loss of dopaminergic tone induced a decrease in TGF-β1 mRNA expression, in active and total cytokine content, and in TGF-β type II receptor expression. Dopamine regulation of pituitary TGF-β1 activation process was inferred by the inhibition of active cytokine by in vivo sulpiride treatment. Interestingly, in the absence of dopaminergic tone, estradiol induced a strong increase in active TGF-β1. PRL secretion correlated with active, but not total cytokine. TGF-β1 inhibitory action on lactotroph proliferation and PRL secretion was decreased in Drd2−/− pituitary cells, in correlation with decreased TGF-β type II receptor. The study of the TGF-β1 activation process and its regulation is essential to understand the cytokine activity. As an intermediary of dopamine inhibition of lactotroph function, TGF-β1 and local activators may be important targets in the treatment of dopamine agonist-resistant prolactinomas.
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Vaz de Castro, Pedro Alves Soares, Pedro A. Jose, and Ana Cristina Simões e Silva. "Interactions between the intrarenal dopaminergic and the renin–angiotensin systems in the control of systemic arterial pressure." Clinical Science 136, no. 16 (August 2022): 1205–27. http://dx.doi.org/10.1042/cs20220338.
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Abstract Systemic arterial hypertension is one of the leading causes of morbidity and mortality in the general population, being a risk factor for many cardiovascular diseases. Although its pathogenesis is complex and still poorly understood, some systems appear to play major roles in its development. This review aims to update the current knowledge on the interaction of the intrarenal renin–angiotensin system (RAS) and dopaminergic system in the development of hypertension, focusing on recent scientific hallmarks in the field. The intrarenal RAS, composed of several peptides and receptors, has a critical role in the regulation of blood pressure (BP) and, consequently, the development of hypertension. The RAS is divided into two main intercommunicating axes: the classical axis, composed of angiotensin-converting enzyme, angiotensin II, and angiotensin type 1 receptor, and the ACE2/angiotensin-(1–7)/Mas axis, which appears to modulate the effects of the classical axis. Dopamine and its receptors are also increasingly showing an important role in the pathogenesis of hypertension, as abnormalities in the intrarenal dopaminergic system impair the regulation of renal sodium transport, regardless of the affected dopamine receptor subtype. There are five dopamine receptors, which are divided into two major subtypes: the D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R) receptors. Mice deficient in any of the five dopamine receptor subtypes have increased BP. Intrarenal RAS and the dopaminergic system have complex interactions. The balance between both systems is essential to regulate the BP homeostasis, as alterations in the control of both can lead to hypertension.
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Boritzki, Vanessa, Harald Hübner, Anni Allikalt, Peter Gmeiner, and Birgitta M. Wöhrl. "Optimizing the Expression of Human Dopamine Receptors in Escherichia coli." International Journal of Molecular Sciences 22, no. 16 (August 11, 2021): 8647. http://dx.doi.org/10.3390/ijms22168647.
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The human dopamine receptors D2S and D3 belong to the group of G protein-coupled receptors (GPCRs) and are important drug targets. Structural analyses and development of new receptor subtype specific drugs have been impeded by low expression yields or receptor instability. Fusing the T4 lysozyme into the intracellular loop 3 improves crystallization but complicates conformational studies. To circumvent these problems, we expressed the human D2S and D3 receptors in Escherichia coli using different N- and C-terminal fusion proteins and thermostabilizing mutations. We optimized expression times and used radioligand binding assays with whole cells and membrane homogenates to evaluate KD-values and the number of receptors in the cell membrane. We show that the presence but not the type of a C-terminal fusion protein is important. Bacteria expressing receptors capable of ligand binding can be selected using FACS analysis and a fluorescently labeled ligand. Improved receptor variants can thus be generated using error-prone PCR. Subsequent analysis of clones showed the distribution of mutations over the whole gene. Repeated cycles of PCR and FACS can be applied for selecting highly expressing receptor variants with high affinity ligand binding, which in the future can be used for analytical studies.
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Shukla, R., VK Khanna, P. Vinod, ML Sankhwar, and RS Yadav. "Platelet Dopamine: D2 Receptor Binding in Patients with Migraine." Cephalalgia 29, no. 5 (May 2009): 532–38. http://dx.doi.org/10.1111/j.1468-2982.2008.01760.x.
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Clinical, genetic and pharmacological evidences suggest an abnormality of the dopaminergic system in the pathogenesis of migraine. Direct evidence of an abnormal metabolism of dopamine in migraine, however, is lacking. Platelets are a useful model to understand brain dopaminergic mechanisms. The present study has been undertaken to study the status of platelet dopamine receptor binding by carrying out radioligand receptor binding assay. Binding of 3H-spiperone to platelet membranes, known to label dopamine (DA)—D2 receptors, was conducted in 20 patients with migraine and an equal number of healthy controls. The equilibrium dissociation constant (Kd) in patients with migraine (1.71 ± 0.19 nM) was found to be significantly lower ( P < 0.001) as compared with controls (3.14 ± 0.33 nM). However, no significant change was observed in the maximal number of binding sites (Bmax) in patients with migraine. No relationship of Kd with type of migraine, presence of vomiting, family history, frequency of attack, duration of illness and menstrual migraine was observed. The findings of the present study provide support for the involvement of the dopaminergic system in migraine.