D1受容体、D1レセプター
WordNet
- the 4th letter of the Roman alphabet (同)d
- a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
PrepTutorEJDIC
- deuteriumの化学記号
- =sense organ / 受信装置
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/23 19:06:02」(JST)
[Wiki en表示]
| Dopamine receptor D1 |
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
|
1OZ5
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| Identifiers |
| Symbols |
DRD1 (; DADR; DRD1A) |
| External IDs |
OMIM: 126449 MGI: 99578 HomoloGene: 30992 IUPHAR: D1 ChEMBL: 2056 GeneCards: DRD1 Gene |
| Gene Ontology |
| Molecular function |
• dopamine neurotransmitter receptor activity, coupled via Gs
• dopamine neurotransmitter receptor activity
• protein binding
• dopamine binding
|
| Cellular component |
• nucleus
• endoplasmic reticulum membrane
• plasma membrane
• integral to plasma membrane
• neuron part
|
| Biological process |
• temperature homeostasis
• conditioned taste aversion
• behavioral fear response
• synaptic transmission, dopaminergic
• response to amphetamine
• protein import into nucleus
• G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• adenylate cyclase-activating G-protein coupled receptor signaling pathway
• activation of adenylate cyclase activity
• adenylate cyclase-activating dopamine receptor signaling pathway
• synapse assembly
• memory
• mating behavior
• grooming behavior
• adult walking behavior
• visual learning
• positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway
• astrocyte development
• dopamine transport
• transmission of nerve impulse
• regulation of action potential in neuron
• dentate gyrus development
• striatum development
• cerebral cortex GABAergic interneuron migration
• positive regulation of cell migration
• peristalsis
• positive regulation of cAMP biosynthetic process
• operant conditioning
• regulation of dopamine metabolic process
• vasodilation
• dopamine metabolic process
• response to drug
• positive regulation of potassium ion transport
• glucose import
• sensitization
• behavioral response to cocaine
• positive regulation of release of sequestered calcium ion into cytosol
• elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway
• regulation of dopamine uptake involved in synaptic transmission
• positive regulation of synaptic transmission, glutamatergic
• prepulse inhibition
• phospholipase C-activating dopamine receptor signaling pathway
• long-term synaptic potentiation
• long term synaptic depression
• cellular response to catecholamine stimulus
|
| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
|
| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
|
| Entrez |
1812 |
13488 |
|
| Ensembl |
ENSG00000184845 |
ENSMUSG00000021478 |
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| UniProt |
P21728 |
Q61616 |
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| RefSeq (mRNA) |
NM_000794 |
NM_010076 |
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| RefSeq (protein) |
NP_000785 |
NP_034206 |
|
| Location (UCSC) |
Chr 5:
174.87 – 174.87 Mb |
Chr 13:
54.05 – 54.06 Mb |
|
| PubMed search |
[1] |
[2] |
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Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.[1][2][3]
Contents
- 1 Function
- 2 Production
- 3 Ligands
- 3.1 Agonists
- 3.2 Antagonists
- 4 Protein-protein interactions
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Function[edit]
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 adenylate cyclase and indirectly activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events.[4] Alternate transcription initiation sites result in two transcript variants of this gene.[5]
Production[edit]
The DRD1 gene expresses primarily in the caudate putamen in humans, and in the caudate putamen, the nucleus accumbens and the olfactory tubercle in mouse. Gene expression patterns from the Allen Brain Atlases in mouse and human can be found here.
Ligands[edit]
There are a number of ligands selective for the D1 receptors. To date, most of the known ligands are based on dihydrexidine or the prototypical benzazepine partial agonist SKF-38393 (one derivative being the prototypical antagonist SCH-23390).[6] None of the known ligands is selective for the D1 vs. the D5 receptor, but the benzazepines generally are more selective for the D1 and D5 receptors versus the D2-like family.[6] Some of the benzazepines have high intrinsic activity whereas others do not.
Agonists[edit]
Chemical structures of selective D
1 receptor agonists.
[7][8]
- Dihydrexidine derivatives
- A-86929 - full agonist with 14-fold selectivity for D1-like receptors over D2[6][8][9]
- Dihydrexidine - full agonist with 10-fold selectivity for D1-like receptors over D2 that has been in Phase IIa clinical trials as a cognitive enhancer.[10][11] It also showed profound antiparkinson effects in MPTP-treated primates,[12] but caused profound hypotension in one early clinical trial in Parkinson's disease.[6] Although dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of functional selectivity[13] with dopamine receptors.[14][15]
- Dinapsoline - full agonist with 5-fold selectivity for D1-like receptors over D2[6]
- Dinoxyline - full agonist with approximately equal affinity for D1-like and D2 receptors[6]
- Doxanthrine - full agonist with 168-fold selectivity for D1-like receptors over D2[6]
- Benzazepine derivatives
- SKF-81297 - 200-fold selectivity for D1 over any other receptor[6]
- SKF-82958 - 57-fold selectivity for D1 over D2[6]
- SKF-38393 - very high selectivity for D1 with negligible affinity for any other receptor[6]
- Fenoldopam - highly selective peripheral D1 receptor partial agonist used clinically as an antihypertensive[6]
- 6-Br-APB - 90-fold selectivity for D1 over D2[6]
- Others
- A-68930
- A-77636
- CY-208,243 - high intrinsic activity partial agonist with moderate selectivity for D1-like over D2-like receptors, member of ergoline ligand family like pergolide and bromocriptine.
- SKF-89145
- SKF-89626
- 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist[16]
- 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[edit]
- Benzazepine derivatives
- SCH-23,390 - 100-fold selectivity for D1 over D5[6]
- SKF-83,959 - 7-fold selectivity for D1 over D5 with negligible affinity for other receptors;[6] 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[6]
Protein-protein interactions[edit]
Dopamine receptor D1 has been shown to interact with COPG,[17] DNAJC14[18] and COPG2.[17]
Receptor oligomers[edit]
The D1 receptor forms heteromers with the following receptors: dopamine D2, D3,[19] histamine H3,[20] μ opioid.[21]
See also[edit]
References[edit]
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 1992. "D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease". The Journal of Neuroscience 12 (10): 3729–3742.
- ^ "Entrez Gene: DRD1 dopamine receptor D1".
- ^ a b c d e f g h i j k l m n o 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Mu Q, Johnson K, Morgan PS, Grenesko EL, Molnar CE, Anderson B, Nahas Z, Kozel FA, Kose S, Knable M, Fernandes P, Nichols DE, Mailman RB, George MS. (2007). "A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia.". Schizophr Res. 94 (1-3): 332–341. doi:10.1016/j.schres.2007.03.033. PMID 17596915.
- ^ George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K, Nahas Z, Knable M, Fernandes P, Juncos J, Huang X, Nichols DE, Mailman RB. (2007). "A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia.". Schizophr Res. 93 (1-3): 42–50. doi:10.1016/j.schres.2007.03.011. PMID 17467956.
- ^ Taylor JR, Lawrence MS, Redmond DE Jr, Elsworth JD, Roth RH, Nichols DE, Mailman RB. (1991). "Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys.". Eur J Pharmacol. 199 (3): 389–391. doi:10.1016/0014-2999(91)90508-N. PMID 1680717.
- ^ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". J. Pharmacol. Exp. Ther. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859.
- ^ Mottola DM, Kilts JD, Lewis MM, Connery HS, Walker QD, Jones SR, Booth RG, Hyslop DK, Piercey M, Wightman RM, Lawler CP, Nichols DE, Mailman RB (June 2002). "Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D2 receptors linked to adenylate cyclase". J. Pharmacol. Exp. Ther. 301 (3): 1166–78. PMID 12023552.
- ^ Kilts JD, Connery HS, Arrington EG, Lewis MM, Lawler CP, Oxford GS, O'Malley KL, Todd RD, Blake BL, Nichols DE, Mailman RB (June 2002). "Functional selectivity of dopamine receptor agonists. II. Actions of dihydrexidine in D2L receptor-transfected MN9D cells and pituitary lactotrophs". J. Pharmacol. Exp. Ther. 301 (3): 1179–89. PMID 12023553.
- ^ Bonner LA, Chemel BR, Watts VJ, Nichols DE (September 2010). "Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists". Bioorg. Med. Chem. 18 (18): 6763–70. doi:10.1016/j.bmc.2010.07.052. PMC 2941879. PMID 20709559.
- ^ 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.
- ^ 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.
- ^ Marcellino D et al (2008): "Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum." J Biol Chem, 283:26016-25. PMID 18644790
- ^ Ferrada C et al (2009): "Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors." Br J Pharmacol, 157:64-75. PMID 19413572
- ^ Juhasz JR et al (2008): "Mu-opioid receptor heterooligomer formation with the dopamine D1 receptor as directly visualized in living cells." Eur J Pharmacol, 581:235-43. PMID 18237729
Further reading[edit]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
External links[edit]
- "Dopamine Receptors: D1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Receptors, Dopamine D1 at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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Cell surface receptor: G protein-coupled receptors
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Class A:
Rhodopsin like |
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| Class B: Secretin like |
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Orphan
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- GPR (56
- 64
- 97
- 98
- 110
- 111
- 112
- 113
- 114
- 115
- 116
- 123
- 124
- 125
- 126
- 128
- 133
- 143
- 144
- 155
- 157)
|
|
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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
- 7
- 8
- 9
- 10
- 13
- 14
- 16
- 19
- 20
- 30
- 31
- 38
- 39
- 40
- 41
- 42
- 43
- 45
- 46
- 50
- 60)
|
|
|
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)
|
|
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Smoothened
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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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Related Links
- 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 ...
- Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn). ... Dopamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on ...
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