Dopamine receptor D2

From Wikipedia, the free encyclopedia
  (Redirected from Dopamine D2 receptor)
Jump to: navigation, search
Dopamine receptor D2
Protein DRD2 PDB 1I15.png
Rendering based on PDB 1I15.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DRD2 ; D2DR; D2R
External IDs OMIM126450 MGI94924 HomoloGene22561 IUPHAR: D2 ChEMBL: 217 GeneCards: DRD2 Gene
RNA expression pattern
PBB GE DRD2 216924 s at tn.png
PBB GE DRD2 206590 x at tn.png
PBB GE DRD2 211624 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1813 13489
Ensembl ENSG00000149295 ENSMUSG00000032259
UniProt P14416 P61168
RefSeq (mRNA) NM_000795 NM_010077
RefSeq (protein) NP_000786 NP_034207
Location (UCSC) Chr 11:
113.28 – 113.35 Mb
Chr 9:
49.34 – 49.41 Mb
PubMed search [1] [2]

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.

Function[edit]

This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity.[citation needed]

In mice, regulation of D2R surface expression by the calcium sensor NCS-1 in the dentate gyrus controls exploration, synaptic plasticity and memory formation.[1]

Isoforms[edit]

Alternative splicing of this gene results in three transcript variants encoding different isoforms.[2]

The long form (D2Lh) has the "canonical" sequence and functions as a classic post-synaptic receptor. The short form (D2Sh) is pre-synaptic and functions as an autoreceptor and regulates the levels of dopamine in the synaptic cleft. Agonism of D2sh receptors inhibits dopamine release; antagonism increases dopaminergic release.[3] A third D2(Longer) form differs from the canonical sequence where 270V is replaced by VVQ.[4]

Genetics[edit]

Allelic variants:

Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism resides in exon 8 of the ANKK1 gene.[8]

Ligands[edit]

Most of the older antipsychotic drugs such as chlorpromazine and haloperidol are antagonists for the dopamine D2 receptor, but are, in general, very unselective, at best selective only for the "D2-like family" receptors and so binding to D2, D3 and D4, and often also to many other receptors such as those for serotonin and histamine, resulting in a range of side-effects and making them poor agents for scientific research. In similar manner, older dopamine agonists used for Parkinson's disease such as bromocriptine and cabergoline are poorly selective for one dopamine receptor over another, and, although most of these agents do act as D2 agonists, they affect other subtypes as well. Several selective D2 ligands are, however, now available, and this number is likely to increase as further research progresses.

Agonists[edit]

Partial agonists[edit]

Antagonists[edit]

D2Sh selective (presynaptic autoreceptors)

Allosteric modulators[edit]

Protein-protein interactions[edit]

The dopamine receptor D2 has been shown to interact with EPB41L1,[17] PPP1R9B[18] and NCS-1.[19]

Receptor oligomers[edit]

The D2 receptor forms heteromers with the following receptors: dopamine D1 (→ D1-D2),[20] D3,[21] 5-HT2A,[22] adenosine A2A,[23] CB1, mGlu5.

See also[edit]

References[edit]

  1. ^ Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC. (2009). "NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory.". Neuron 63 (5): 643–56. doi:10.1016/j.neuron.2009.08.014. PMID 19755107. 
  2. ^ "Entrez Gene: DRD2 dopamine receptor D2". 
  3. ^ Cooper DC. "Neuromodulation". Introduction to Neuroscience I. Boulder Colorado: University of Colorado at Boulder. p. 90. 
  4. ^ UniProt P14416
  5. ^ Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV (February 2003). "Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor". Hum. Mol. Genet. 12 (3): 205–16. doi:10.1093/hmg/ddg055. PMID 12554675. 
  6. ^ Arinami T, Gao M, Hamaguchi H, Toru M (April 1997). "A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia". Hum. Mol. Genet. 6 (4): 577–82. doi:10.1093/hmg/6.4.577. PMID 9097961. 
  7. ^ Glatt SJ, Faraone SV, Tsuang MT (July 2004). "DRD2 -141C insertion/deletion polymorphism is not associated with schizophrenia: results of a meta-analysis". Am. J. Med. Genet. B Neuropsychiatr. Genet. 128B (1): 21–3. doi:10.1002/ajmg.b.30007. PMID 15211624. 
  8. ^ Lucht M, Rosskopf D (July 2008). "Comment on "Genetically determined differences in learning from errors"". Science 321 (5886): 200; author reply 200. doi:10.1126/science.1155372. PMID 18621654. 
  9. ^ "Clinical Pharmacology for Abilify". RxList.com. 2010-01-21. Retrieved 2010-01-21. 
  10. ^ Holmes IP, Blunt RJ, Lorthioir OE, Blowers SM, Gribble A, Payne AH, Stansfield IG, Wood M, Woollard PM, Reavill C, Howes CM, Micheli F, Di Fabio R, Donati D, Terreni S, Hamprecht D, Arista L, Worby A, Watson SP (March 2010). "The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure". Bioorganic & Medicinal Chemistry Letters 20 (6): 2013–6. doi:10.1016/j.bmcl.2010.01.090. PMID 20153647. 
  11. ^ Giacomelli S, Palmery M, Romanelli L, Cheng CY, Silvestrini B (1998). "Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro". Life Sci. 63 (3): 215–22. doi:10.1016/S0024-3205(98)00262-8. PMID 9698051. 
  12. ^ Wang GJ, Volkow ND, Thanos PK, Fowler JS (2004). "Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review". J Addict Dis 23 (3): 39–53. doi:10.1300/J069v23n03_04. PMID 15256343. 
  13. ^ Huang, R; Griffin, SA; Taylor, M; Vangveravong, S; Mach, RH; Dillon, GH; Luedtke, RR (2013). "The effect of SV 293, a D2 dopamine receptor-selective antagonist, on D2 receptor-mediated GIRK channel activation and adenylyl cyclase inhibition.". Pharmacology 92 (1-2): 84–9. doi:10.1159/000351971. PMID 23942137. 
  14. ^ Agnati, LF; Ferré, S; Genedani, S; Leo, G; Guidolin, D; Filaferro, M; Carriba, P; Casadó, V; Lluis, C; Franco, R; Woods, AS; Fuxe, K (Nov 2006). "Allosteric modulation of dopamine D2 receptors by homocysteine.". Journal of proteome research 5 (11): 3077–83. doi:10.1021/pr0601382. PMID 17081059. 
  15. ^ Beyaert MG, Daya RP, Dyck BA, Johnson RL, Mishra RK (2012). "PAOPA, a potent dopamine D2 receptor allosteric modulator, prevents and reverses behavioral and biochemical abnormalities in an amphetamine-sensitized preclinical animal model of schizophrenia". Eur Neuropsychopharmacol 23 (3): 253–62. doi:10.1016/j.euroneuro.2012.04.010. PMID 22658400. 
  16. ^ Silvano E, Millan MJ, Mannoury la Cour C, et al. (2010). "The tetrahydroisoquinoline derivative SB269,652 is an allosteric antagonist at dopamine D3 and D2 receptors". Mol. Pharmacol. 78 (5): 925–34. doi:10.1124/mol.110.065755. PMC 2981362. PMID 20702763. 
  17. ^ Binda AV, Kabbani N, Lin R, Levenson R (September 2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Mol. Pharmacol. 62 (3): 507–13. doi:10.1124/mol.62.3.507. PMID 12181426. 
  18. ^ Smith FD, Oxford GS, Milgram SL (July 1999). "Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein". J. Biol. Chem. 274 (28): 19894–900. doi:10.1074/jbc.274.28.19894. PMID 10391935. 
  19. ^ Kabbani N, Negyessy L, Lin R, Goldman-Rakic, Levenson R. (2002). "Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor.". J. Neurosci. 22 (19): 8476–86. PMID 12351722. 
  20. ^ Hasbi A, O'Dowd BF, George SR (2011): "Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance", Mol Brain, 26. PMID 21663703
  21. ^ Maggio R, Millan MJ (2010). "Dopamine D2-D3 receptor heteromers: pharmacological properties and therapeutic significance". Current Opinion in Pharmacology 10 (1): 100–7. doi:10.1016/j.coph.2009.10.001. 
  22. ^ Albizu L, Holloway T, González-Maeso J, Sealfon SC (2011). "Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors". Neuropharmacology 61 (4): 770–7. doi:10.1016/j.neuropharm.2011.05.023. PMID 21645528. 
  23. ^ Kamiya T, Saitoh O, Yoshioka K, Nakata H (June 2003). "Oligomerization of adenosine A2A and dopamine D2 receptors in living cells". Biochem. Biophys. Res. Commun. 306 (2): 544–9. doi:10.1016/S0006-291X(03)00991-4. PMID 12804599. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.