Dopamine receptor D1

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Dopamine receptor D1
Identifiers
Symbols	DRD1; DADR; DRD1A
External IDs	OMIM: 126449 MGI: 99578 HomoloGene: 30992 IUPHAR: D1 GeneCards: DRD1 Gene
Gene Ontology Molecular function • rhodopsin-like receptor activity • dopamine D1 receptor activity • receptor activity • dopamine receptor activity Cellular component • cell • membrane fraction • plasma membrane • integral to plasma membrane Biological process • signal transduction • G-protein signaling, coupled to cyclic nucleotide second messenger • adenylate cyclase activation • dopamine receptor, adenylate cyclase activating pathway • elevation of cytosolic calcium ion concentration • synaptic transmission • nervous system development • mating behavior • locomotory behavior • response to drug Sources: Amigo / EGO
RNA expression pattern
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1812	13488
Ensembl	ENSG00000184845	ENSMUSG00000021478
UniProt	P21728	Q80T33
RefSeq (mRNA)	NM_000794	NM_010076
RefSeq (protein)	NP_000785	NP_034206
Location (UCSC)	Chr 5: 174.8 - 174.8 Mb	Chr 13: 54.06 - 54.07 Mb
PubMed search	[1]	[2]

Dopamine receptor D₁, also known as DRD1, is a protein which in humans is encoded by the DRD1 gene.

Function

This gene encodes the D₁ subtype of the dopamine receptor. The D₁ subtype is the most abundant dopamine receptor in the central nervous system. This G-protein coupled receptor stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases. D₁ receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D₂-mediated events. Alternate transcription initiation sites result in two transcript variants of this gene.

Ligands

There are a number of ligands selective for the D₁ receptors. They comprise almost exclusively of compounds derived from dihydrexidine and from the prototypical benzazepine SCH-23,390. While the benzazepines are generally highly and fully selective for the D₁ receptor over all other receptors, the dihydrexidine derivatives do not distinguish between the D₁ and D₅ receptors and therefore cannot be said to be truly selective. The benzazepines are weak partial agonists/antagonists with low intrinsic activity, while the dihydrexidine derivatives function as full agonists with intrinsic activity equal to or greater than that elicited by dopamine itself.

Agonists

• Dihydrexidine derivatives
  • A-86,929 - full agonist with 14-fold selectivity for D₁-like receptors over D₂
  • Dihydrexidine - full agonist with 10-fold selectivity for D₁-like receptors over D₂ that was being investigated for the treatment of Parkinson's disease but was discontinued due to intolerable side effects
  • Dinapsoline - full agonist with 5-fold selectivity for D₁-like receptors over D₂
  • Dinoxyline - full agonist with approximately equal affinity for D₁-like and D₂ receptors
  • Doxanthrine - full agonist with 168-fold selectivity for D₁-like receptors over D₂

• Benzazepine derivatives
  • SKF-81,297 - 200-fold selectivity for D₁ over any other receptor
  • SKF-82,958 - 57-fold selectivity for D₁ over D₂
  • SKF-38,393 - very high selectivity for D₁ with negligible affinity for any other receptor
  • Fenoldopam - highly selective peripheral D₁ receptor partial agonist used clinically as an antihypertensive
  • 6-Br-APB - 90-fold selectivity for D₁ over D₂
• Others
  • A-68,930
  • A-77,636
  • CY-208,243 - partial agonist with moderate selectivity for D₁-like over D₂-like receptors, structurally most closely related to ergoline-based dopamine agonists like pergolide.
  • SKF-89,145
  • SKF-89,626

• • Cabergoline - weak D₁ agonism, highly selective for D₂, and various serotonin receptors
  • Pergolide - (similar to cabergoline) weak D₁ agonism, highly selective for D₂, and various serotonin receptors

Antagonists

• Benzazepine derivatives
  • SCH-23,390 - 100-fold selectivity for D₁ over D₅
  • SKF-83,959 - 7-fold selectivity for D₁ over D₅ with negligible affinity for other receptors; acts as an antagonist at D₁ but as an agonist at D₅
  • Ecopipam (SCH-39,166) - a selective D₁/D₅ antagonist that was being developed as an anti-obesity medication but was discontinued

Interactions

Dopamine receptor D1 has been shown to interact with COPG, DNAJC14 and COPG2.

See also

• Dopamine receptor

Further reading

• Missale C, Nash SR, Robinson SW; et al. (1998). "Dopamine receptors: from structure to function". Physiol. Rev. 78 (1): 189–225. PMID 9457173. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Milligan G, White JH (2001). "Protein-protein interactions at G-protein-coupled receptors". Trends Pharmacol. Sci. 22 (10): 513–8. doi:10.1016/S0165-6147(00)01801-0. PMID 11583808. 
• Bermak JC, Zhou QY (2004). "Accessory proteins in the biogenesis of G protein-coupled receptors". Mol. Interv. 1 (5): 282–7. PMID 14993367. 
• Minowa MT, Minowa T, Monsma FJ; et al. (1992). "Characterization of the 5' flanking region of the human D1A dopamine receptor gene". Proc. Natl. Acad. Sci. U.S.A. 89 (7): 3045–9. doi:10.1073/pnas.89.7.3045. PMC 48800 Freely accessible. PMID 1557411. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Tiberi M, Jarvie KR, Silvia C; et al. (1991). "Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor". Proc. Natl. Acad. Sci. U.S.A. 88 (17): 7491–5. doi:10.1073/pnas.88.17.7491. PMC 52326 Freely accessible. PMID 1831904. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sunahara RK, Niznik HB, Weiner DM; et al. (1990). "Human dopamine D1 receptor encoded by an intronless gene on chromosome 5". Nature. 347 (6288): 80–3. doi:10.1038/347080a0. PMID 1975640. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Grandy DK, Zhou QY, Allen L; et al. (1990). "A human D1 dopamine receptor gene is located on chromosome 5 at q35.1 and identifies an EcoRI RFLP". Am. J. Hum. Genet. 47 (5): 828–34. PMC 1683700 Freely accessible. PMID 1977312. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Dearry A, Gingrich JA, Falardeau P; et al. (1990). "Molecular cloning and expression of the gene for a human D1 dopamine receptor". Nature. 347 (6288): 72–6. doi:10.1038/347072a0. PMID 2144334. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Zhou QY, Grandy DK, Thambi L; et al. (1990). "Cloning and expression of human and rat D1 dopamine receptors". Nature. 347 (6288): 76–80. doi:10.1038/347076a0. PMID 2168520. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Frail DE, Manelli AM, Witte DG; et al. (1994). "Cloning and characterization of a truncated dopamine D1 receptor from goldfish retina: stimulation of cyclic AMP production and calcium mobilization". Mol. Pharmacol. 44 (6): 1113–8. PMID 8264547. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ohara K, Ulpian C, Seeman P; et al. (1993). "Schizophrenia: dopamine D1 receptor sequence is normal, but has DNA polymorphisms". Neuropsychopharmacology. 8 (2): 131–5. PMID 8471124. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Albrecht FE, Drago J, Felder RA; et al. (1996). "Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension". J. Clin. Invest. 97 (10): 2283–8. doi:10.1172/JCI118670. PMC 507308 Freely accessible. PMID 8636408. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Lee SH, Minowa MT, Mouradian MM (1996). "Two distinct promoters drive transcription of the human D1A dopamine receptor gene". J. Biol. Chem. 271 (41): 25292–9. doi:10.1074/jbc.271.41.25292. PMID 8810292. CS1 maint: Multiple names: authors list (link)
• Mayerhofer A, Hemmings HC, Snyder GL; et al. (1999). "Functional dopamine-1 receptors and DARPP-32 are expressed in human ovary and granulosa luteal cells in vitro". J. Clin. Endocrinol. Metab. 84 (1): 257–64. doi:10.1210/jc.84.1.257. PMID 9920093. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Wong AC, Shetreat ME, Clarke JO, Rayport S (1999). "D1- and D2-like dopamine receptors are co-localized on the presynaptic varicosities of striatal and nucleus accumbens neurons in vitro". Neuroscience. 89 (1): 221–33. doi:10.1016/S0306-4522(98)00284-X. PMID 10051231. CS1 maint: Multiple names: authors list (link)
• Jin H, Xie Z, George SR, O'Dowd BF (2000). "Palmitoylation occurs at cysteine 347 and cysteine 351 of the dopamine D(1) receptor". Eur. J. Pharmacol. 386 (2-3): 305–12. doi:10.1016/S0014-2999(99)00727-X. PMID 10618483. CS1 maint: Multiple names: authors list (link)
• Li M, Bermak JC, Wang ZW, Zhou QY (2000). "Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280)". Mol. Pharmacol. 57 (3): 446–52. PMID 10692483. CS1 maint: Multiple names: authors list (link)
• Lezcano N, Mrzljak L, Eubanks S; et al. (2000). "Dual signaling regulated by calcyon, a D1 dopamine receptor interacting protein". Science. 287 (5458): 1660–4. doi:10.1126/science.287.5458.1660. PMID 10698743. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ginés S, Hillion J, Torvinen M; et al. (2000). "Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes". Proc. Natl. Acad. Sci. U.S.A. 97 (15): 8606–11. doi:10.1073/pnas.150241097. PMC 26995 Freely accessible. PMID 10890919. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• "Dopamine Receptors: D₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
• MeSH Receptors,+Dopamine+D1

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

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