Dopamine receptor D2

Dopamine receptor D2

Rendering based on PDB 1I15.
Identifiers
Symbols DRD2; D2DR; D2R
External IDs OMIM126450 MGI94924 HomoloGene22561 IUPHAR: D2 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 Q0VGH9
RefSeq (mRNA) NM_000795.3 NM_010077.2
RefSeq (protein) NP_000786.1 NP_034207.2
Location (UCSC) Chr 11:
113.28 – 113.35 Mb
Chr 9:
49.15 – 49.22 Mb
PubMed search [1] [2]

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

Contents

Function

This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia.[1]

Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing.[2]

Genetics

Allelic variants:

  • A-241G
  • C132T, G423A, T765C, C939T, C957T, and G1101A [3]
  • Cys311Ser
  • -141C insertion/deletion[4]

The polymorphisms has been investigated with respect to association with schizophrenia.[5]

Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism sits in exon 8 of the ANKK1 gene.[6]

Ligands

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

Antagonists

D2Sh selective (presynaptic autoreceptors)

Interactions

Dopamine receptor D2 has been shown to interact with Adenosine A2A receptor,[12] EPB41L1[13] and PPP1R9B.[14]

See also

References

  1. ^ "Gene Overview of All Published Schizophrenia-Association Studies for DRD2". Schizophrenia Research Forum. 2009-03-26. http://www.schizophreniaforum.org/res/sczgene/geneoverview.asp?geneid=93. Retrieved 2009-06-09. 
  2. ^ "Entrez Gene: DRD2 dopamine receptor D2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1813. 
  3. ^ http://hmg.oxfordjournals.org/content/12/3/205.short
  4. ^ T. Arinami, M. Gao, H. Hamaguchi, M. Toru (1997). "A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia". Human Molecular Genetics 6 (4): 577–582. doi:10.1093/hmg/6.4.577. PMID 9097961. 
  5. ^ 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. 
  6. ^ M. Lucht, D. Rosskopf (July 2008). "Comment on "Genetically determined differences in learning from errors"". Science 321 (5886): 200. doi:10.1126/science.1155372. PMID 18621654. http://www.sciencemag.org/cgi/content/full/321/5886/200a. 
  7. ^ "Clinical Pharmacology for Abilify". RxList.com. 2010-01-21. http://www.rxlist.com/abilify-drug.htm. Retrieved 2010-01-21. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ http://ajp.psychiatryonline.org/cgi/content/abstract/156/6/876
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 

Further reading

External links

Metabolites and
signaling molecules
Peptide
Miscellaneous
Class B: Secretin like Class C: Metabotropic
glutamate / pheromone Class F:
Frizzled / Smoothened
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

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