Dopamine receptor D1

Dopamine receptor D1
Identifiers
Symbols	DRD1; DADR; DRD1A
External IDs	OMIM: 126449 MGI: 99578 HomoloGene: 30992 GeneCards: DRD1 Gene
Gene Ontology Molecular function • dopamine receptor activity, coupled via Gs • dopamine receptor activity, coupled via Gs • dopamine D1 receptor activity • receptor activity • G-protein coupled receptor activity • dopamine receptor activity • protein binding • drug binding • dopamine binding Cellular component • membrane fraction • nucleus • endoplasmic reticulum • endoplasmic reticulum membrane • plasma membrane • plasma membrane • plasma membrane • integral to plasma membrane • caveola • axon • neuronal cell body • dendritic spine Biological process • temperature homeostasis • conditioned taste aversion • behavioral fear response • synaptic transmission, dopaminergic • response to amphetamine • negative regulation of protein kinase activity • protein import into nucleus • intracellular protein transport • muscle contraction • G-protein signaling, coupled to cyclic nucleotide second messenger • activation of adenylate cyclase activity by G-protein signaling pathway • activation of adenylate cyclase activity • activation of adenylate cyclase activity by dopamine receptor signaling pathway • synapse assembly • memory • mating behavior • grooming behavior • locomotory behavior • adult walking behavior • visual learning • astrocyte development • dopamine transport • transmission of nerve impulse • regulation of action potential in neuron • calcium-mediated signaling • dentate gyrus development • striatum development • cerebral cortex GABAergic interneuron migration • positive regulation of cell migration • negative regulation of cell migration • peristalsis • positive regulation of cAMP biosynthetic process • phosphatidylinositol catabolic process • cellular response to insulin stimulus • operant conditioning • regulation of dopamine metabolic process • negative regulation of circadian sleep/wake cycle, sleep • dopamine metabolic process • response to drug • eating behavior • positive regulation of potassium ion transport • regulation of ion transport • glucose import • sensitization • behavioral response to cocaine • regulation of long-term neuronal synaptic plasticity • positive regulation of release of sequestered calcium ion into cytosol • elevation of cytosolic calcium ion concentration involved in G-protein signaling coupled to IP3 second messenger • regulation of dopamine uptake • positive regulation of synaptic transmission, glutamatergic • prepulse inhibition • activation of phospholipase C activity by dopamine receptor signaling pathway • activation of phospholipase C activity by dopamine receptor signaling pathway • long-term synaptic potentiation • long term synaptic depression Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1812	13488
Ensembl	ENSG00000184845	ENSMUSG00000021478
UniProt	P21728	Q80T33
RefSeq (mRNA)	NM_000794.3	NM_010076.3
RefSeq (protein)	NP_000785.1	NP_034206.1
Location (UCSC)	Chr 5: 174.87 – 174.87 Mb	Chr 13: 54.15 – 54.15 Mb
PubMed search	[1]	[2]

Dopamine receptor D₁, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.^[1][2][3]

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^{[citation needed]}. Alternate transcription initiation sites result in two transcript variants of this gene.^[4]

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.^[5] 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.^[5] The benzazepines are weak partial agonists/antagonists with low intrinsic activity, whereas the dihydrexidine derivatives function as full agonists with intrinsic activity equal to or greater than that elicited by dopamine itself.^[5]

Agonists

Chemical structures of selective D₁ receptor agonists.<^[6][7]

• Dihydrexidine derivatives
  • A-86,929 - full agonist with 14-fold selectivity for D₁-like receptors over D₂^[5][7][8]
  • 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^[5]
  • Dinapsoline - full agonist with 5-fold selectivity for D₁-like receptors over D₂^[5]
  • Dinoxyline - full agonist with approximately equal affinity for D₁-like and D₂ receptors^[5]
  • Doxanthrine - full agonist with 168-fold selectivity for D₁-like receptors over D₂^[5]

• Benzazepine derivatives
  • SKF-81,297 - 200-fold selectivity for D₁ over any other receptor^[5]
  • SKF-82,958 - 57-fold selectivity for D₁ over D₂^[5]
  • SKF-38,393 - very high selectivity for D₁ with negligible affinity for any other receptor^[5]
  • Fenoldopam - highly selective peripheral D₁ receptor partial agonist used clinically as an antihypertensive^[5]
  • 6-Br-APB - 90-fold selectivity for D₁ over D₂^[5]
• 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
  • 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist^[9]

• • 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^[5]
  • SKF-83,959 - 7-fold selectivity for D₁ over D₅ with negligible affinity for other receptors;^[5] 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^[5]

Interactions

Dopamine receptor D1 has been shown to interact with COPG,^[10] DNAJC14^[11] and COPG2.^[10]

See also

• Dopamine receptor

References

1. ^ Dearry A, Gingrich JA, Falardeau P, Fremeau RT, Bates MD, Caron MG (September 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. 
2. ^ Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HH, Cone R, Pribnow D, Salon J, Bunzow JR, Civelli O (September 1990). "Cloning and expression of human and rat D₁dopamine receptors". Nature 347 (6288): 76–80. doi:10.1038/347076a0. PMID 2168520. 
3. ^ Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL, Gelernter JE, Rozmahel R, Yang YL, Israel Y, O'Dowd BF. (September 1990). "Human dopamine D₁ receptor encoded by an intronless gene on chromosome 5". Nature 347 (6288): 80–3. doi:10.1038/347080a0. PMID 1975640. 
4. ^ "Entrez Gene: DRD1 dopamine receptor D₁". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1812. 
5. ^ ^{a b c d e f g h i j k l m n o p} Zhang J, Xiong B, Zhen X, Zhang A. (2009). "Dopamine D₁ receptor ligands: where are we now and where are we going.". Med Res Rev. 29 (2): 272–294. doi:10.1002/med.20130. PMID 18642350. 
6. ^ Cueva JP, Giorgioni G, Grubbs RA, Chemel BR, Watts VJ, Nichols DE (November 2006). "trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist". J. Med. Chem. 49 (23): 6848–57. doi:10.1021/jm0604979. PMID 17154515. 
7. ^ ^{a b} Michaelides MR, Hong Y, DiDomenico S, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K (1995). "(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D₁agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431)". J. Med. Chem. 38 (18): 3445–7. doi:10.1021/jm00018a002. PMID 7658429. 
8. ^ Yamashita M, Yamada K, Tomioka K (2004). "Construction of arene-fused-piperidine motifs by asymmetric addition of 2-trityloxymethylaryllithiums to nitroalkenes: the asymmetric synthesis of a dopamine D₁ full agonist, A-86929". J. Am. Chem. Soc. 126 (7): 1954–5. doi:10.1021/ja031760n. PMID 14971926. 
9. ^ PMID 20709559
10. ^ ^{a b} Bermak, Jason C; Li Ming, Bullock Clayton, Weingarten Paul, Zhou Qun-Yong (Feb. 2002). "Interaction of gamma-COP with a transport motif in the D1 receptor C-terminus". Eur. J. Cell Biol. (Germany) 81 (2): 77–85. doi:10.1078/0171-9335-00222. ISSN 0171-9335. PMID 11893085. 
11. ^ Bermak, J C; Li M, Bullock C, Zhou Q Y (May. 2001). "Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein". Nat. Cell Biol. (England) 3 (5): 492–8. doi:10.1038/35074561. ISSN 1465-7392. PMID 11331877. 

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. 
• 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. PMID 1557411. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48800. 
• 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. PMID 1831904. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=52326. 
• 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. 
• 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. PMID 1977312. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683700. 
• 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. 
• 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. 
• 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. 
• 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. 
• 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. PMID 8636408. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=507308. 
• 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. 
• 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. 
• 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. 
• 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. 
• 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. 
• 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. 
• 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. PMID 10890919. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26995. 

External links

• "Dopamine Receptors: D₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2252. 
• MeSH Receptors,+Dopamine+D1

Metabolites and
signaling molecules

Eicosanoid	CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane
Other	Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate  · Lysophosphatidic acid (1, 2, 3, 4, 5, 6)  · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate

Peptide

Neuropeptide	B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)
Other	Anaphylatoxin (C3a, C5a) · Angiotensin (1, 2) · Apelin · Bombesin (BRS3, GRPR, NMBR) · Bradykinin (B1, B2) · Chemokine · Cholecystokinin (A, B) · Endothelin (A, B) · Formyl peptide (1, 2, 3) · FSH · Galanin (1, 2, 3) · GHB receptor · Gonadotropin-releasing hormone (1, 2) · Ghrelin · Kisspeptin · Luteinizing hormone/choriogonadotropin · MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) · Melanocortin (1, 2, 3, 4, 5) · MCHR (1, 2) · Motilin · Opioid (Delta, Kappa, Mu, Nociceptin & Zeta, but not Sigma) · Orexin (1, 2) · Oxytocin · Prokineticin (1, 2) · Prolactin-releasing peptide · Relaxin (1, 2, 3, 4) · Somatostatin (1, 2, 3, 4, 5) · Tachykinin (1, 2, 3) · Thyrotropin · Thyrotropin-releasing hormone · Urotensin-II · Vasopressin (1A, 1B, 2)

Miscellaneous

Orphan	GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Other	Adrenomedullin · Olfactory · Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) · Protease-activated (1, 2, 3, 4) · SREB (1, 2, 3)

Class B: Secretin like

Orphan	GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Other	Brain-specific angiogenesis inhibitor (1, 2, 3) · Cadherin (1, 2, 3) · Calcitonin · CALCRL · CD97 · Corticotropin-releasing hormone (1, 2) · EMR (1, 2, 3) · Glucagon (GR, GIPR, GLP1R, GLP2R) · Growth hormone releasing hormone · PACAPR1 · GPR · Latrophilin (1, 2, 3, ELTD1) · Methuselah-like proteins · Parathyroid hormone (1, 2) · Secretin · Vasoactive intestinal peptide (1, 2)

Class C: Metabotropic
glutamate / pheromone

Taste	TAS1R (1, 2, 3) · TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Other	Calcium-sensing receptor · GABA B (1, 2) · Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR (156, 158, 179) · RAIG (1, 2, 3, 4)

Class F:
Frizzled / Smoothened

Frizzled	Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Smoothened	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)