Genomes and Genes
Gene Symbol: Drd2
Description: dopamine receptor D2
Alias: D(2) dopamine receptor, dopamine receptor 2
- Sokoloff P, Giros B, Martres M, Bouthenet M, Schwartz J. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990;347:146-51 pubmed..It seems to mediate some of the effects of antipsychotic drugs and drugs used against Parkinson's disease, that were previously thought to interact only with D2 receptors. ..
- Kim O, Ariano M, Namkung Y, Marinec P, Kim E, Han J, et al. D2 dopamine receptor expression and trafficking is regulated through direct interactions with ZIP. J Neurochem. 2008;106:83-95 pubmed publisher..These results suggest that ZIP can physically interact with the D(2) DAR leading to increased intracellular trafficking to lysosomes with subsequent down-regulation of receptor expression and function. ..
- Van Ham I, Banihashemi B, Wilson A, Jacobsen K, Czesak M, Albert P. Differential signaling of dopamine-D2S and -D2L receptors to inhibit ERK1/2 phosphorylation. J Neurochem. 2007;102:1796-1804 pubmed publisher..In conclusion, the D(2)S and D(2)L receptors differ in inhibitory signaling to ERK1/2 due to specific residues in the D(2)L receptor alternatively spliced domain, which may account for differences in their function in vivo. ..
- Nair V, Olanow C, Sealfon S. Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines. Biochem J. 2003;373:25-32 pubmed..These studies indicate that certain dopamine agonists can complex with D(2) receptors to preferentially transactivate neuroprotective signalling pathways and to mediate increased cell survival. ..
- Saiardi A, Bozzi Y, Baik J, Borrelli E. Antiproliferative role of dopamine: loss of D2 receptors causes hormonal dysfunction and pituitary hyperplasia. Neuron. 1997;19:115-26 pubmed..These results point to prolactin as an autocrine proliferative factor in the pituitary gland. Additionally, they demonstrate an antiproliferative function for DA regulated through D2 receptor activation. ..
- Wang Y, Xu R, Sasaoka T, Tonegawa S, Kung M, Sankoorikal E. Dopamine D2 long receptor-deficient mice display alterations in striatum-dependent functions. J Neurosci. 2000;20:8305-14 pubmed..This suggests that the functions of these two isoforms are not dependent on the formation of receptor heterodimers. Our findings may provide novel information for potentially developing improved antipsychotic drugs. ..
- Caine S, Negus S, Mello N, Patel S, Bristow L, Kulagowski J, et al. Role of dopamine D2-like receptors in cocaine self-administration: studies with D2 receptor mutant mice and novel D2 receptor antagonists. J Neurosci. 2002;22:2977-88 pubmed..Our results also suggest that D3 and D4 receptors do not play major roles in the modulation of cocaine self-administration by D2-like drugs. ..
- Welter M, Vallone D, Samad T, Meziane H, Usiello A, Borrelli E. Absence of dopamine D2 receptors unmasks an inhibitory control over the brain circuitries activated by cocaine. Proc Natl Acad Sci U S A. 2007;104:6840-5 pubmed..Our findings show that the absence of D2R, very likely through a presynaptic mechanism, uncovers an inhibitory signaling pathway normally masked by the activity of this receptor on brain circuitries engaged by abused drugs. ..
- Schmitz Y, Schmauss C, Sulzer D. Altered dopamine release and uptake kinetics in mice lacking D2 receptors. J Neurosci. 2002;22:8002-9 pubmed..These results from D2-null mutant mice support the suggestion that D2 autoreceptors and dopamine transporters interact to regulate the amplitude and timing of dopamine signals. ..
- Bailey A, Metaxas A, Yoo J, McGee T, Kitchen I. Decrease of D2 receptor binding but increase in D2-stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose 'binge' cocaine administration paradigm. Eur J Neurosci. 2008;28:759-70 pubmed publisher
- Guiramand J, Montmayeur J, Ceraline J, Bhatia M, Borrelli E. Alternative splicing of the dopamine D2 receptor directs specificity of coupling to G-proteins. J Biol Chem. 1995;270:7354-8 pubmed..Our analysis identified two mutants, S259/262A and D249V, with these properties. These results clearly show that the insert present in D2L plays a critical role in the selectivity for the G-proteins interacting with the receptor. ..
- Liu X, Chu X, Mao L, Wang M, Lan H, Li M, et al. Modulation of D2R-NR2B interactions in response to cocaine. Neuron. 2006;52:897-909 pubmed..This type of dopamine-glutamate integration at the receptor level may be responsible for synergistically inhibiting the D2R-mediated circuits in the basal ganglia and fulfilling the stimulative effect of psychostimulants. ..
- Dickinson S, Sabeti J, Larson G, Giardina K, Rubinstein M, Kelly M, et al. Dopamine D2 receptor-deficient mice exhibit decreased dopamine transporter function but no changes in dopamine release in dorsal striatum. J Neurochem. 1999;72:148-56 pubmed..These results further strengthen the idea that the D2 DA receptor subtype modulates activity of the striatal DAT. ..
- Jeanneteau F, Diaz J, Sokoloff P, Griffon N. Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors. Mol Biol Cell. 2004;15:696-705 pubmed..Through its dimerization, GIPC acts as a selective scaffold protein to assist receptor functions. Our results suggest a novel function for GIPC in the maintenance, trafficking, and signaling of GPCRs. ..
- An J, Cho S, Jeong D, Park K, Ahn Y, Baik J. Anti-proliferative effects and cell death mediated by two isoforms of dopamine D2 receptors in pituitary tumor cells. Mol Cell Endocrinol. 2003;206:49-62 pubmed..These results suggest that dopamine induces an anti-proliferative effect and cell death via the dopamine D2 receptors, by means of the p38 MAPK and ERK pathways involving oxidative stress, in the pituitary tumor cells. ..
- Sarkar D, Chaturvedi K, Oomizu S, Boyadjieva N, Chen C. Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-beta1, and TGF-beta type II receptor interact to inhibit the growth of pituitary lactotropes. Endocrinology. 2005;146:4179-88 pubmed..The constitutive expression of D2 receptor short isoform also reduced the tumor cell growth rate. These data suggest that a TGFbeta1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes. ..
- Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett D, Bach A, et al. The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J. 1989;8:4025-34 pubmed..Both receptors expressed in cultured mammalian cells bind [3H]spiperone with high affinity and inhibit adenylyl cyclase, as expected of the D2 receptor subtype. ..
- Binda A, Kabbani N, Levenson R. Regulation of dense core vesicle release from PC12 cells by interaction between the D2 dopamine receptor and calcium-dependent activator protein for secretion (CAPS). Biochem Pharmacol. 2005;69:1451-61 pubmed..These results suggest that D2 dopamine receptors may modulate vesicle release from neuroendocrine cells via direct interaction with components of the exocytotic machinery. ..
- Coffeen U, López Avila A, Ortega Legaspi J, del Angel R, López Muñoz F, Pellicer F. Dopamine receptors in the anterior insular cortex modulate long-term nociception in the rat. Eur J Pain. 2008;12:535-43 pubmed..This work shows the differential role of dopamine receptors within the RAIC in which the activation of D(2) or the blockade of D(1) receptors elicit antinociception. ..
- Briand L, Flagel S, Seeman P, Robinson T. Cocaine self-administration produces a persistent increase in dopamine D2 High receptors. Eur Neuropsychopharmacol. 2008;18:551-6 pubmed publisher..This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine. ..
- Koyanagi S, Himukashi S, Mukaida K, Shichino T, Fukuda K. Dopamine D2-like receptor in the nucleus accumbens is involved in the antinociceptive effect of nitrous oxide. Anesth Analg. 2008;106:1904-9 pubmed publisher..It is possible that inhalation of N(2)O activates mesolimbic dopaminergic neurons, and that the antinociceptive effect of N(2)O is at least partially mediated by dopamine D(2)-like receptors in the NAc shell region. ..
- Baik J, Picetti R, Saiardi A, Thiriet G, Dierich A, Depaulis A, et al. Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors. Nature. 1995;377:424-8 pubmed..Our study shows that D2 receptors have a key role in the dopaminergic control of nervous function. These mice have therapeutic potential as a model for investigating and correcting dysfunctions of the dopaminergic system. ..
- Montmayeur J, Bausero P, Amlaiky N, Maroteaux L, Hen R, Borrelli E. Differential expression of the mouse D2 dopamine receptor isoforms. FEBS Lett. 1991;278:239-43 pubmed..Membranes of mammalian cells transiently transfected with both forms of D2 receptor bind [3H]spiperone with a high affinity. ..
- Minowa T, Minowa M, Mouradian M. Analysis of the promoter region of the rat D2 dopamine receptor gene. Biochemistry. 1992;31:8389-96 pubmed..Unlike the D1A gene, however, the D2 gene has a strong preference for transcription initiation to three consecutive nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Calabresi P, Saiardi A, Pisani A, Baik J, Centonze D, Mercuri N, et al. Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. J Neurosci. 1997;17:4536-44 pubmed..This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease. ..
- Dalley J, Fryer T, Brichard L, Robinson E, Theobald D, Laane K, et al. Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science. 2007;315:1267-70 pubmed..These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences. ..
- Rouge Pont F, Usiello A, Benoit Marand M, Gonon F, Piazza P, Borrelli E. Changes in extracellular dopamine induced by morphine and cocaine: crucial control by D2 receptors. J Neurosci. 2002;22:3293-301 pubmed..Thus, deregulated expression of D2R isoforms might be involved in the vulnerability of an individual to drug abuse. ..
- Smith F, Oxford G, Milgram S. Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. J Biol Chem. 1999;274:19894-900 pubmed..We hypothesize that spinophilin is important for establishing a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors to downstream signaling molecules and the actin cytoskeleton. ..
- Zhang X, Bedigian A, Wang W, Eggert U. G protein-coupled receptors participate in cytokinesis. Cytoskeleton (Hoboken). 2012;69:810-8 pubmed publisher..Understanding the molecular details of GPCRs and their interaction proteins in cytokinesis regulation will give us important clues about GPCRs signaling as well as how cells communicate with their environment during division. ..
- Barnard N, Noble E, Ritchie T, Cohen J, Jenkins D, Turner McGrievy G, et al. D2 dopamine receptor Taq1A polymorphism, body weight, and dietary intake in type 2 diabetes. Nutrition. 2009;25:58-65 pubmed publisher..01) significantly less than did A1(-) individuals. The A1 allele appears to be highly prevalent among individuals with type 2 diabetes. Potential influences on diet, weight, and glycemic control merit further exploration. ..
- Marley A, von Zastrow M. DISC1 regulates primary cilia that display specific dopamine receptors. PLoS ONE. 2010;5:e10902 pubmed publisher..Our findings provide new insight to receptor cell biology and suggest a relationship between DISC1 and neural dopamine signaling. ..
- Chawla A, Cordner Z, Boersma G, Moran T. Cognitive impairment and gene expression alterations in a rodent model of binge eating disorder. Physiol Behav. 2017;180:78-90 pubmed publisher..Finally, in the nucleus accumbens (NAc), we found decreased dopamine receptor 2 (Drd2) expression among BEP rats...
- Fitzgerald M, Mackie K, Pickel V. The impact of adolescent social isolation on dopamine D2 and cannabinoid CB1 receptors in the adult rat prefrontal cortex. Neuroscience. 2013;235:40-50 pubmed publisher..This suggests a biological mechanism whereby the adolescent social environment can persistently influence cortical dopaminergic activity and resultant behavior. ..
- Xu H, Chen R, Cai X, He D. Differential effects of activating D1 and D2 receptors on electrophysiology of neostriatal neurons in a rat model of Parkinson's disease induced by paraquat and maneb. Neurosci Res. 2011;71:411-20 pubmed publisher..Our results illustrate the electrophysiological changes of in vivo neostriatal neurons in Parkinson's disease, thereby providing insight into the regulatory mechanisms of dopamine-mediated physiology. ..
- Alcantara A, Chen V, Herring B, Mendenhall J, Berlanga M. Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. Brain Res. 2003;986:22-9 pubmed
- Solinas M, Tanda G, Wertheim C, Goldberg S. Dopaminergic augmentation of delta-9-tetrahydrocannabinol (THC) discrimination: possible involvement of D(2)-induced formation of anandamide. Psychopharmacology (Berl). 2010;209:191-202 pubmed publisher..Dopamine does not play a major role in THC discrimination. However, activation of the dopaminergic system positively modulates the discriminative effects of THC, possibly through D(2)-induced elevations in brain levels of anandamide. ..
- Onali P, Olianas M, Gessa G. Characterization of dopamine receptors mediating inhibition of adenylate cyclase activity in rat striatum. Mol Pharmacol. 1985;28:138-45 pubmed..The results indicate that in rat striatum dopamine inhibits adenylate cyclase activity by acting on postsynaptic dopamine receptors with pharmacological properties of D2 type. ..
- Risinger F, Freeman P, Rubinstein M, Low M, Grandy D. Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. Psychopharmacology (Berl). 2000;152:343-50 pubmed..Reduced responding in the KO mice for several reinforcers including ethanol indicates a more general role for dopamine D2 receptors in motivated responding rather than a specific role in ethanol reinforcement. ..
- Seo S, Lomberk G, Mathison A, Buttar N, Podratz J, Calvo E, et al. Krüppel-like factor 11 differentially couples to histone acetyltransferase and histone methyltransferase chromatin remodeling pathways to transcriptionally regulate dopamine D2 receptor in neuronal cells. J Biol Chem. 2012;287:12723-35 pubmed publisher..2) and MODY VII (maturity onset diabetes of the young VII), regulates transcription of the fopamine D2 receptor (Drd2) gene...
- Otth C, Torres M, Ramirez A, Fernandez J, Castro M, Rauch M, et al. Novel identification of peripheral dopaminergic D2 receptor in male germ cells. J Cell Biochem. 2007;100:141-50 pubmed..The presence of D2R receptors in male germ cells implies new and unsuspected roles for dopamine signaling in testicular and sperm physiology. ..
- Qin Z, Chen J, Weiss B. Lesions of mouse striatum induced by 6-hydroxydopamine differentially alter the density, rate of synthesis, and level of gene expression of D1 and D2 dopamine receptors. J Neurochem. 1994;62:411-20 pubmed
- Fedotova I. [Stimulation of D2-receptors improves passive avoidance learning in female rats]. Patol Fiziol Eksp Ter. 2012;:53-6 pubmed..The results of the study suggest modulating role of D2-receptors in learning/memory processes during ovary cycle in the adult female rats. ..
- Kabbani N, Jeromin A, Levenson R. Dynamin-2 associates with the dopamine receptor signalplex and regulates internalization of activated D2 receptors. Cell Signal. 2004;16:497-503 pubmed..Taken together, our findings suggest that dynamin-2 regulates D2R internalization and thus is likely to play an important role in D2R mediated dopaminergic transmission. ..
- An J, Bae M, Cho S, Lee S, Choi S, Lee B, et al. Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors. Mol Cell Neurosci. 2004;25:732-41 pubmed
- Thanos P, Taintor N, Rivera S, Umegaki H, Ikari H, Roth G, et al. DRD2 gene transfer into the nucleus accumbens core of the alcohol preferring and nonpreferring rats attenuates alcohol drinking. Alcohol Clin Exp Res. 2004;28:720-8 pubmedTransient overexpression of the dopamine D2 receptor (DRD2) gene in the nucleus accumbens (NAc) using an adenoviral vector has been associated with a significant decrease in alcohol intake in Sprague Dawley rats...
- Asa S, Kelly M, Grandy D, Low M. Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice. Endocrinology. 1999;140:5348-55 pubmed..The unexpected development of adenomas in males without preexisting or concomitant hyperplasia suggests that prolonged loss of dopamine inhibition may also cause neoplasia by distinct cellular mechanisms in male and female animals. ..