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维基百科

多巴胺受體D2

行進 23, 2023

维基百科中的醫學内容仅供参考，並不能視作專業意見。如需獲取醫療幫助或意見，请咨询专业人士。詳見醫學聲明。

多巴胺受體D2（Dopamine receptor D2，簡稱D2R），為轉譯自 DRD2 基因的一種多巴胺受體蛋白。D2R最早於1975年為Philip Seeman（英语：Philip Seeman）所發現，並將其命名為「抗精神疾患性多巴胺受體」（antipsychotic dopamine receptor）[6]。D2R為所有抗精神病药物的作用標的。

多巴胺受體D2
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名DRD2；, D2DR, D2R, dopamine receptor D2
外部IDOMIM：126450 MGI：94924 HomoloGene：22561 GeneCards：DRD2
為以下藥物的標靶
benzquinamide、​LP-12、​LP-211、​LP-44、​力必平、​羅替戈汀、​维拉佐酮、​7-hydroxy-2-(di-N-propylamino)tetralin、​溴隱亭、​多巴胺、​培高利特、​普拉克索、​quinelorane、​quinpirole、​sumanirole、​阿樸嗎啡、​阿立哌唑、​brexpiprazole、​過乳降、​麥角乙脲、​吡貝地爾、​roxindole、​terguride、​氨磺必利、​布南色林、​(+)-butaclamol、​氯丙嗪、​氯氮平、​多潘立酮、​eticlopride、​三氟噻噸、​氟奋乃静、​氟哌啶醇、​L-741,626、​洛沙平、​mesoridazine、​nafadotride、​奥氮平、​perospirone、​奋乃静、​匹莫齊特、​pipotiazine、​普樂明、​promazine、​喹硫平、​raclopride、​維思通、​sertindole、​舒必利、​levosulpiride、​三氟拉嗪、​齊拉西酮、​zotepine[1]
基因位置（人类）
染色体11號染色體[2]
基因座11q23.2起始113,409,605 bp[2]
终止113,475,691 bp[2]
RNA表达模式




查阅更多表达数据
直系同源
物種人類小鼠
Entrez

1813

13489

Ensembl

ENSG00000149295

ENSMUSG00000032259

UniProt

P14416

P61168

mRNA​序列

NM_016574
​NM_000795

NM_010077

蛋白序列

NP_000786
​NP_057658
NP_000786.1

NP_034207

基因位置​（UCSC）Chr 11: 113.41 – 113.48 MbChr 9: 49.25 – 49.32 Mb
PubMed​查找[4][5]
維基數據
檢視/編輯人類檢視/編輯小鼠

功能

D2R屬於一種多巴胺受體，並會與Gi結合。Gi為G蛋白偶联受体的一種亞型，會抑制腺苷酸环化酶的活性[7]。

在小鼠模式中，齒狀回的neuronal calcium sensor-1（英语：neuronal calcium sensor-1）（NCS-1）會影響D2R在細胞膜的表現量。這項機制會影響突触可塑性及記憶形成[8]。

在蒼蠅模式中，多巴胺性神經元上的D2R自體受器（英语：autoreceptor）能避免神經元死亡，進而引發類帕金森氏症的症狀[9]。

同型體

Alternative splicing of this gene results in three transcript variants encoding different isoform（英语：isoform）s.[10]

The long form (D2Lh) has the "canonical" sequence and functions as a classic post-synaptic receptor.[11]The short form (D2Sh) is pre-synaptic and functions as an autoreceptor（英语：autoreceptor） that regulates the levels of dopamine in the synaptic cleft.[11]Agonism of D2sh receptors inhibits dopamine release; antagonism increases dopaminergic（英语：dopaminergic） release.[11]A third D2(Longer) form differs from the canonical sequence where 270V is replaced by VVQ.[12]

基因組

等位基因變異：

  • A-241G
  • C132T、G423A、T765C、C939T、C957T（英语：C957T），以及G1101A[13]
  • Cys311Ser
  • -141C insertion/deletion[14]The polymorphisms have been investigated with respect to association with schizophrenia.[15]

Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism resides in exon 8 of the ANKK1（英语：ANKK1） gene.[16]DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinson's disease.[17][18]

配體

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（英语：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.

受體致活劑

  • 溴隱亭（Bromocriptine）：完全受體致活劑
  • Cabergoline（英语：Cabergoline）（Caberl）
  • N,N-Propyldihydrexidine：D1/D5受體制活劑dihydrexidine（英语：dihydrexidine）的類似物，對節後神經元的D2R親和性比節前神經元的D2自體受器（英语：autoreceptor）高。
  • Piribedil（英语：Piribedil）：同時也是 D3 受體致活劑及腎上腺素α2受體拮抗劑（英语：α2-adrenergic receptor）
  • Pramipexole（英语：Pramipexole）：同時也是D3、D4受體致活劑
  • Quinelorane（英语：Quinelorane）：affinity for D2 > D3
  • Quinpirole（英语：Quinpirole）：同時也是D3受體致活劑
  • Ropinirole（英语：Ropinirole）：完全受體致活劑
  • Sumanirole（英语：Sumanirole）：高選擇性完全受體致活劑
  • Talipexole（英语：Talipexole）：對D2的親和性高於其他的多巴胺受體，但同時也是腎上腺素α2受體制活劑及5-HT3受體拮抗劑。

部分受體致活劑

  • Aplindore（英语：Aplindore）
  • 阿立哌唑（Aripiprazole，在美國合法）[19]
  • Brexpiprazole（英语：Brexpiprazole）/OPC-34712（英语：OPC-34712）
  • Cariprazine（英语：Cariprazine）
  • RP5063（英语：RP5063）
  • GSK-789,472（英语：GSK-789,472） – Also D3 antagonist, with good selectivity over other receptors [20]
  • 氯胺酮（Ketamine，同時也為NMDA受體拮抗劑）
  • LSD – in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs.[21]LSD is also a 5-HT2A agonist.
  • 莫达非尼（Modafinil）
  • Roxindole（英语：Roxindole） (only at the D2 autoreceptors)
  • OSU-6162（英语：OSU-6162）：亦為5-HT2A部分受體致活劑，acts as "dopamine stabilizer"
  • Salvinorin A（英语：Salvinorin A）：亦為κ-鴉片類受體致活劑（英语：Κ-opioid receptor）。

受體拮抗劑

  • Atypical antipsychotics（英语：Atypical antipsychotics）
  • Desmethoxyfallypride（英语：Desmethoxyfallypride）
  • Domperidone – D2 and D3 antagonist; does not cross the blood-brain barrier
  • Eticlopride（英语：Eticlopride）
  • Fallypride（英语：Fallypride）
  • Hydroxyzine (Vistaril, Atarax)
  • Itopride（英语：Itopride）
  • L-741,626（英语：L-741,626） – highly selective D2 antagonist
  • C11 Raclopride（英语：Raclopride） radiolabled – commonly employed in positron emission tomography studies[22]
  • Typical antipsychotics（英语：Typical antipsychotics）
  • SV 293[23]
  • Yohimbine
D2sh selective (presynaptic autoreceptors)

異位調控因子

Functionally selective ligands

  • 參見參考文獻[29]。

Protein–protein interactions

The dopamine receptor D2 has been shown to interact with EPB41L1（英语：EPB41L1）,[30]PPP1R9B（英语：PPP1R9B）[31]and NCS-1（英语：NCS-1）.[32]

Receptor oligomers

The D2 receptor forms receptor heterodimers（英语：GPCR oligomer） in vivo (in living animals) with other G protein-coupled receptors; these include:[33]

  • D1–D2 dopamine receptor heteromer（英语：D1–D2 dopamine receptor heteromer）
  • D2–adenosine A2A
  • D2–ghrelin receptor（英语：ghrelin receptor）
  • D2sh–TAAR1（英语：TAAR1）[note 1]

The D2 receptor has been shown to form hetorodimers in vitro (and possibly in vivo) with DRD3（英语：Dopamine D3 receptor）,[36]DRD5（英语：Dopamine receptor D5）,[37]and 5-HT2A（英语：5-HT2A receptor）.[38]

註釋

  1. ^ D2sh–TAAR1 is a presynaptic heterodimer which involves the relocation of TAAR1 from the intracellular space to D2sh at the plasma membrane, increased D2sh agonist binding affinity, and signal transduction through the calcium–PKC–NFAT（英语：NFAT） pathway and G-protein independent PKB–GSK3（英语：GSK3） pathway.[34][35]

參考文獻

  1. ^ 對dopamine receptor D2起作用的藥物；在維基數據上查看/編輯參考. 
  2. ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000149295 - Ensembl, May 2017
  3. ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000032259 - Ensembl, May 2017
  4. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ Madras BK. History of the discovery of the antipsychotic dopamine D2 receptor: a basis for the dopamine hypothesis of schizophrenia. Journal of the History of the Neurosciences. 2013, 22 (1): 62–78. PMID 23323533. doi:10.1080/0964704X.2012.678199. 
  7. ^ Usiello A, Baik JH, Rougé-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E. Distinct functions of the two isoforms of dopamine D2 receptors. Nature. Nov 2000, 408 (6809): 199–203. PMID 11089973. doi:10.1038/35041572. 
  8. ^ Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC. NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory. Neuron. Sep 2009, 63 (5): 643–56. PMID 19755107. doi:10.1016/j.neuron.2009.08.014. 
  9. ^ Wiemerslage L, Schultz BJ, Ganguly A, Lee D. Selective degeneration of dopaminergic neurons by MPP(+) and its rescue by D2 autoreceptors in Drosophila primary culture. Journal of Neurochemistry. Aug 2013, 126 (4): 529–40. PMID 23452092. doi:10.1111/jnc.12228. 
  10. ^ Entrez Gene: DRD2 dopamine receptor D2. （原始内容于2010-03-07）. 
  11. ^ 11.0 11.1 11.2 Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacological Reviews. Mar 2011, 63 (1): 182–217. PMID 21303898. doi:10.1124/pr.110.002642. 
  12. ^ UniProt P14416
  13. ^ Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Human Molecular Genetics. Feb 2003, 12 (3): 205–16. PMID 12554675. doi:10.1093/hmg/ddg055. 
  14. ^ Arinami T, Gao M, Hamaguchi H, Toru M. A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Human Molecular Genetics. Apr 1997, 6 (4): 577–82. PMID 9097961. doi:10.1093/hmg/6.4.577. 
  15. ^ Glatt SJ, Faraone SV, Tsuang MT. DRD2 -141C insertion/deletion polymorphism is not associated with schizophrenia: results of a meta-analysis. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. Jul 2004, 128B (1): 21–3. PMID 15211624. doi:10.1002/ajmg.b.30007. 
  16. ^ Lucht M, Rosskopf D. Comment on "Genetically determined differences in learning from errors". Science. Jul 2008, 321 (5886): 200; author reply 200. PMID 18621654. doi:10.1126/science.1155372. 
  17. ^ Wang J, Liu ZL, Chen B. Association study of dopamine D2, D3 receptor gene polymorphisms with motor fluctuations in PD. Neurology. Jun 2001, 56 (12): 1757–9. PMID 11425949. doi:10.1212/WNL.56.12.1757. 
  18. ^ Wang J, Zhao C, Chen B, Liu ZL. Polymorphisms of dopamine receptor and transporter genes and hallucinations in Parkinson's disease. Neuroscience Letters. Jan 2004, 355 (3): 193–6. PMID 14732464. doi:10.1016/j.neulet.2003.11.006. 
  19. ^ Clinical Pharmacology for Abilify. RxList.com. 2010-01-21 [2010-01-21]. （原始内容于2010-01-18）. 
  20. ^ 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. The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure. Bioorganic & Medicinal Chemistry Letters. Mar 2010, 20 (6): 2013–6. PMID 20153647. doi:10.1016/j.bmcl.2010.01.090. 
  21. ^ Giacomelli S, Palmery M, Romanelli L, Cheng CY, Silvestrini B. Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro. Life Sciences. 1998, 63 (3): 215–22. PMID 9698051. doi:10.1016/S0024-3205(98)00262-8. 
  22. ^ Wang GJ, Volkow ND, Thanos PK, Fowler JS. Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review. Journal of Addictive Diseases. 2004, 23 (3): 39–53. PMID 15256343. doi:10.1300/J069v23n03_04. 
  23. ^ Huang R, Griffin SA, Taylor M, Vangveravong S, Mach RH, Dillon GH, Luedtke RR. The effect of SV 293, a D2 dopamine receptor-selective antagonist, on D2 receptor-mediated GIRK channel activation and adenylyl cyclase inhibition. Pharmacology. 2013, 92 (1–2): 84–9. PMID 23942137. doi:10.1159/000351971. 
  24. ^ Agnati LF, Ferré S, Genedani S, Leo G, Guidolin D, Filaferro M, Carriba P, Casadó V, Lluis C, Franco R, Woods AS, Fuxe K. Allosteric modulation of dopamine D2 receptors by homocysteine. Journal of Proteome Research. Nov 2006, 5 (11): 3077–83. PMID 17081059. doi:10.1021/pr0601382. 
  25. ^ Beyaert MG, Daya RP, Dyck BA, Johnson RL, Mishra RK. PAOPA, a potent dopamine D2 receptor allosteric modulator, prevents and reverses behavioral and biochemical abnormalities in an amphetamine–sensitized preclinical animal model of schizophrenia. European Neuropsychopharmacology. Mar 2013, 23 (3): 253–62. PMID 22658400. doi:10.1016/j.euroneuro.2012.04.010. 
  26. ^ Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. A new mechanism of allostery in a G protein–coupled receptor dimer. Nature Chemical Biology. Sep 2014, 10 (9): 745–52. PMID 25108820. doi:10.1038/nchembio.1593. 
  27. ^ Maggio R, Scarselli M, Capannolo M, Millan MJ. Novel dimensions of D3 receptor function: Focus on heterodimerisation, transactivation and allosteric modulation. European Neuropsychopharmacology. Sep 2015, 25 (9): 1470–9. PMID 25453482. doi:10.1016/j.euroneuro.2014.09.016. 
  28. ^ Silvano E, Millan MJ, Mannoury la Cour C, Han Y, Duan L, Griffin SA, Luedtke RR, Aloisi G, Rossi M, Zazzeroni F, Javitch JA, Maggio R. The tetrahydroisoquinoline derivative SB269,652 is an allosteric antagonist at dopamine D3 and D2 receptors. Molecular Pharmacology. Nov 2010, 78 (5): 925–34. PMC 2981362  . PMID 20702763. doi:10.1124/mol.110.065755. 
  29. ^ Möller D, Kling RC, Skultety M, Leuner K, Hübner H, Gmeiner P. Functionally selective dopamine D₂, D₃ receptor partial agonists. Journal of Medicinal Chemistry. Jun 2014, 57 (11): 4861–75. PMID 24831693. doi:10.1021/jm5004039. 
  30. ^ Binda AV, Kabbani N, Lin R, Levenson R. D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N. Molecular Pharmacology. Sep 2002, 62 (3): 507–13. PMID 12181426. doi:10.1124/mol.62.3.507. 
  31. ^ Smith FD, Oxford GS, Milgram SL. Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. The Journal of Biological Chemistry. Jul 1999, 274 (28): 19894–900. PMID 10391935. doi:10.1074/jbc.274.28.19894. 
  32. ^ Kabbani N, Negyessy L, Lin R, Goldman-Rakic P, Levenson R. Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. The Journal of Neuroscience. Oct 2002, 22 (19): 8476–86. PMID 12351722. 
  33. ^ Beaulieu JM, Espinoza S, Gainetdinov RR. Dopamine receptors - IUPHAR Review 13. British Journal of Pharmacology. Jan 2015, 172 (1): 1–23. PMC 4280963  . PMID 25671228. doi:10.1111/bph.12906. 
  34. ^ Grandy DK, Miller GM, Li JX. "TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference. Drug Alcohol Depend. February 2016, 159: 9–16. PMID 26644139. doi:10.1016/j.drugalcdep.2015.11.014. This original observation of TAAR1 and DA D2R interaction has subsequently been confirmed and expanded upon with observations that both receptors can heterodimerize with each other under certain conditions ... Additional DA D2R/TAAR1 interactions with functional consequences are revealed by the results of experiments demonstrating that in addition to the cAMP/PKA pathway (Panas et al., 2012) stimulation of TAAR1-mediated signaling is linked to activation of the Ca++/PKC/NFAT pathway (Panas et al.,2012) and the DA D2R-coupled, G protein-independent AKT/GSK3 signaling pathway (Espinoza et al., 2015; Harmeier et al., 2015), such that concurrent TAAR1 and DA DR2R activation could result in diminished signaling in one pathway (e.g. cAMP/PKA) but retention of signaling through another (e.g., Ca++/PKC/NFA) 
  35. ^ Harmeier A, Obermueller S, Meyer CA, Revel FG, Buchy D, Chaboz S, Dernick G, Wettstein JG, Iglesias A, Rolink A, Bettler B, Hoener MC. Trace amine-associated receptor 1 activation silences GSK3β signaling of TAAR1 and D2R heteromers. Eur Neuropsychopharmacol. 2015, 25 (11): 2049–61. PMID 26372541. doi:10.1016/j.euroneuro.2015.08.011. Interaction of TAAR1 with D2R altered the subcellular localization of TAAR1 and increased D2R agonist binding affinity. 
  36. ^ Maggio R, Millan MJ. Dopamine D2-D3 receptor heteromers: pharmacological properties and therapeutic significance. Current Opinion in Pharmacology. Feb 2010, 10 (1): 100–7. PMID 19896900. doi:10.1016/j.coph.2009.10.001. 
  37. ^ Hasbi A, O'Dowd BF, George SR. Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms. Current Opinion in Pharmacology. Feb 2010, 10 (1): 93–9. PMC 2818238  . PMID 19897420. doi:10.1016/j.coph.2009.09.011. 
  38. ^ Albizu L, Holloway T, González-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology. Sep 2011, 61 (4): 770–7. PMC 3556730  . PMID 21645528. doi:10.1016/j.neuropharm.2011.05.023. 

外部連結

  • 醫學主題詞表（MeSH）：Receptors,+Dopamine+D2
  • Pappas, Stephanie. Study: Genes Influence Who Your Friends Are. Imaginova Corp. LiveScience. [20 January 2011]. 


多巴胺受體D2引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

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行進 23, 2023
多巴胺受體d, 维基百科中的醫學内容仅供参考, 並不能視作專業意見, 如需獲取醫療幫助或意見, 请咨询专业人士, 詳見醫學聲明, 多巴胺受體d2, dopamine, receptor, 簡稱d2r, 為轉譯自, drd2, 基因的一種多巴胺受體蛋白, d2r最早於1975年為philip, seeman, 英语, philip, seeman, 所發現, 並將其命名為, 抗精神疾患性多巴胺受體, antipsychotic, dopamine, receptor, d2r為所有抗精神病药物的作用標的, 多巴胺受體. 维基百科中的醫學内容仅供参考 並不能視作專業意見 如需獲取醫療幫助或意見 请咨询专业人士 詳見醫學聲明 多巴胺受體D2 Dopamine receptor D2 簡稱D2R 為轉譯自 DRD2 基因的一種多巴胺受體蛋白 D2R最早於1975年為Philip Seeman 英语 Philip Seeman 所發現 並將其命名為 抗精神疾患性多巴胺受體 antipsychotic dopamine receptor 6 D2R為所有抗精神病药物的作用標的 多巴胺受體D2已知的結構PDB直系同源搜索 PDBe RCSBPDBID列表6CM4識別號别名DRD2 D2DR D2R dopamine receptor D2外部IDOMIM 126450 MGI 94924 HomoloGene 22561 GeneCards DRD2為以下藥物的標靶benzquinamide LP 12 LP 211 LP 44 力必平 羅替戈汀 维拉佐酮 7 hydroxy 2 di N propylamino tetralin 溴隱亭 多巴胺 培高利特 普拉克索 quinelorane quinpirole sumanirole 阿樸嗎啡 阿立哌唑 brexpiprazole 過乳降 麥角乙脲 吡貝地爾 roxindole terguride 氨磺必利 布南色林 butaclamol 氯丙嗪 氯氮平 多潘立酮 eticlopride 三氟噻噸 氟奋乃静 氟哌啶醇 L 741 626 洛沙平 mesoridazine nafadotride 奥氮平 perospirone 奋乃静 匹莫齊特 pipotiazine 普樂明 promazine 喹硫平 raclopride 維思通 sertindole 舒必利 levosulpiride 三氟拉嗪 齊拉西酮 zotepine 1 基因位置 人类 染色体11號染色體 2 基因座11q23 2起始113 409 605 bp 2 终止113 475 691 bp 2 基因位置 小鼠 染色体小鼠9号染色体 3 基因座9 A5 3 9 26 72 cM起始49 251 927 bp 3 终止49 319 477 bp 3 RNA表达模式查阅更多表达数据基因本體分子功能 protein homodimerization activity potassium channel regulator activity dopamine neurotransmitter receptor activity coupled via Gi Go 相同蛋白质结合 dopamine neurotransmitter receptor activity G protein coupled receptor activity 血浆蛋白结合 signal transducer activity adrenergic receptor activity dopamine binding signaling receptor binding ionotropic glutamate receptor binding protein heterodimerization activity細胞組分 cytoplasmic vesicle sperm flagellum endocytic vesicle 顶体 树突棘 synaptic vesicle membrane 細胞本體 细胞膜 树突 ciliary membrane axon terminus integral component of membrane 突触后致密物质 膜 lateral plasma membrane 轴突 胞內 non motile cilium integral component of plasma membrane dopaminergic synapse glutamatergic synapse GABA ergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane生物學過程 negative regulation of cell population proliferation temperature homeostasis adenylate cyclase inhibiting dopamine receptor signaling pathway adenohypophysis development circadian regulation of gene expression response to toxic substance regulation of dopamine secretion response to cocaine response to amphetamine sensory perception of smell locomotory behavior positive regulation of urine volume response to ethanol axonogenesis response to inactivity phospholipase C activating dopamine receptor signaling pathway modulation of chemical synaptic transmission 个人仪容 negative regulation of protein kinase B signaling associative learning positive regulation of cytosolic calcium ion concentration involved in phospholipase C activating G protein coupled signaling pathway regulation of dopamine uptake involved in synaptic transmission regulation of synaptic transmission GABAergic positive regulation of dopamine uptake involved in synaptic transmission 訊息傳遞 Wnt信号通路 adult walking behavior branching morphogenesis of a nerve negative regulation of cytosolic calcium ion concentration negative regulation of innate immune response regulation of phosphoprotein phosphatase activity acid secretion feeding behavior positive regulation of G protein coupled receptor signaling pathway response to axon injury striatum development synaptic transmission dopaminergic nervous system process involved in regulation of systemic arterial blood pressure 蠕動 regulation of long term neuronal synaptic plasticity activation of protein kinase activity positive regulation of growth hormone secretion regulation of sodium ion transport forebrain development response to light stimulus orbitofrontal cortex development prepulse inhibition response to morphine response to iron ion positive regulation of ERK1 and ERK2 cascade 长期记忆 positive regulation of renal sodium excretion negative regulation of insulin secretion neuron neuron synaptic transmission intracellular signal transduction auditory behavior behavioral response to ethanol regulation of heart rate adenylate cyclase activating adrenergic receptor signaling pathway positive regulation of cytokinesis regulation of potassium ion transport pigmentation cellular calcium ion homeostasis dopamine metabolic process response to nicotine regulation of MAPK cascade response to histamine negative regulation of synaptic transmission glutamatergic response to hypoxia negative regulation of circadian sleep wake cycle sleep negative regulation of protein secretion synapse assembly regulation of locomotion involved in locomotory behavior dopamine receptor signaling pathway negative regulation of dopamine receptor signaling pathway 驚跳反射 positive regulation of receptor internalization protein localization arachidonic acid secretion positive regulation of transcription by RNA polymerase II G protein coupled receptor internalization positive regulation of multicellular organism growth positive regulation of long term synaptic potentiation negative regulation of dopamine secretion adult behavior cerebral cortex GABAergic interneuron migration regulation of synapse structural plasticity adenylate cyclase modulating G protein coupled receptor signaling pathway visual learning negative regulation of cell migration behavioral response to cocaine positive regulation of neuroblast proliferation negative regulation of blood pressure release of sequestered calcium ion into cytosol negative regulation of voltage gated calcium channel activity G protein coupled receptor signaling pathway negative regulation of adenylate cyclase activity 興奮性動作電位 negative regulation of protein phosphorylation 自噬 positive regulation of neurogenesis negative regulation of cell death drinking behavior adrenergic receptor signaling pathway regulation of neurotransmitter uptake postsynaptic modulation of chemical synaptic transmission regulation of synaptic vesicle exocytosisSources Amigo QuickGO直系同源物種人類小鼠Entrez181313489EnsemblENSG00000149295ENSMUSG00000032259UniProtP14416P61168mRNA 序列NM 016574 NM 000795NM 010077蛋白序列NP 000786 NP 057658NP 000786 1NP 034207基因位置 UCSC Chr 11 113 41 113 48 MbChr 9 49 25 49 32 MbPubMed 查找 4 5 維基數據檢視 編輯人類檢視 編輯小鼠 目录 1 功能 2 同型體 3 基因組 4 配體 4 1 受體致活劑 4 2 部分受體致活劑 4 3 受體拮抗劑 4 4 異位調控因子 4 5 Functionally selective ligands 5 Protein protein interactions 5 1 Receptor oligomers 6 註釋 7 參考文獻 8 外部連結功能 编辑D2R屬於一種多巴胺受體 並會與Gi結合 Gi為G蛋白偶联受体的一種亞型 會抑制腺苷酸环化酶的活性 7 在小鼠模式中 齒狀回的neuronal calcium sensor 1 英语 neuronal calcium sensor 1 NCS 1 會影響D2R在細胞膜的表現量 這項機制會影響突触可塑性及記憶形成 8 在蒼蠅模式中 多巴胺性神經元上的D2R自體受器 英语 autoreceptor 能避免神經元死亡 進而引發類帕金森氏症的症狀 9 同型體 编辑Alternative splicing of this gene results in three transcript variants encoding different isoform 英语 isoform s 10 The long form D2Lh has the canonical sequence and functions as a classic post synaptic receptor 11 The short form D2Sh is pre synaptic and functions as an autoreceptor 英语 autoreceptor that regulates the levels of dopamine in the synaptic cleft 11 Agonism of D2sh receptors inhibits dopamine release antagonism increases dopaminergic 英语 dopaminergic release 11 A third D2 Longer form differs from the canonical sequence where 270V is replaced by VVQ 12 基因組 编辑等位基因變異 A 241G C132T G423A T765C C939T C957T 英语 C957T 以及G1101A 13 Cys311Ser 141C insertion deletion 14 The polymorphisms have been investigated with respect to association with schizophrenia 15 Some researchers have previously associated the polymorphism Taq 1A rs1800497 to the DRD2 gene However the polymorphism resides in exon 8 of the ANKK1 英语 ANKK1 gene 16 DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinson s disease 17 18 配體 编辑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 英语 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 受體致活劑 编辑 溴隱亭 Bromocriptine 完全受體致活劑 Cabergoline 英语 Cabergoline Caberl N N Propyldihydrexidine D1 D5受體制活劑dihydrexidine 英语 dihydrexidine 的類似物 對節後神經元的D2R親和性比節前神經元的D2自體受器 英语 autoreceptor 高 Piribedil 英语 Piribedil 同時也是 D3 受體致活劑及腎上腺素a2受體拮抗劑 英语 a2 adrenergic receptor Pramipexole 英语 Pramipexole 同時也是D3 D4受體致活劑 Quinelorane 英语 Quinelorane affinity for D2 gt D3 Quinpirole 英语 Quinpirole 同時也是D3受體致活劑 Ropinirole 英语 Ropinirole 完全受體致活劑 Sumanirole 英语 Sumanirole 高選擇性完全受體致活劑 Talipexole 英语 Talipexole 對D2的親和性高於其他的多巴胺受體 但同時也是腎上腺素a2受體制活劑及5 HT3受體拮抗劑 部分受體致活劑 编辑 Aplindore 英语 Aplindore 阿立哌唑 Aripiprazole 在美國合法 19 Brexpiprazole 英语 Brexpiprazole OPC 34712 英语 OPC 34712 Cariprazine 英语 Cariprazine RP5063 英语 RP5063 GSK 789 472 英语 GSK 789 472 Also D3 antagonist with good selectivity over other receptors 20 氯胺酮 Ketamine 同時也為NMDA受體拮抗劑 LSD in vitro LSD was found to be a partial agonist and potentiates dopamine mediated prolactin secretion in lactotrophs 21 LSD is also a 5 HT2A agonist 莫达非尼 Modafinil Roxindole 英语 Roxindole only at the D2 autoreceptors OSU 6162 英语 OSU 6162 亦為5 HT2A部分受體致活劑 acts as dopamine stabilizer Salvinorin A 英语 Salvinorin A 亦為k 鴉片類受體致活劑 英语 K opioid receptor 受體拮抗劑 编辑 Atypical antipsychotics 英语 Atypical antipsychotics Desmethoxyfallypride 英语 Desmethoxyfallypride Domperidone D2 and D3 antagonist does not cross the blood brain barrier Eticlopride 英语 Eticlopride Fallypride 英语 Fallypride Hydroxyzine Vistaril Atarax Itopride 英语 Itopride L 741 626 英语 L 741 626 highly selective D2 antagonist C11 Raclopride 英语 Raclopride radiolabled commonly employed in positron emission tomography studies 22 Typical antipsychotics 英语 Typical antipsychotics SV 293 23 YohimbineD2sh selective presynaptic autoreceptors Amisulpride low doses UH 232 英语 UH 232 異位調控因子 编辑 Homocysteine 負向異位調控因子 英语 allosteric modulator 24 PAOPA 25 SB 269 652 26 27 28 Functionally selective ligands 编辑 參見參考文獻 29 Protein protein interactions 编辑The dopamine receptor D2 has been shown to interact with EPB41L1 英语 EPB41L1 30 PPP1R9B 英语 PPP1R9B 31 and NCS 1 英语 NCS 1 32 Receptor oligomers 编辑 The D2 receptor forms receptor heterodimers 英语 GPCR oligomer in vivo in living animals with other G protein coupled receptors these include 33 D1 D2 dopamine receptor heteromer 英语 D1 D2 dopamine receptor heteromer D2 adenosine A2A D2 ghrelin receptor 英语 ghrelin receptor D2sh TAAR1 英语 TAAR1 note 1 The D2 receptor has been shown to form hetorodimers in vitro and possibly in vivo with DRD3 英语 Dopamine D3 receptor 36 DRD5 英语 Dopamine receptor D5 37 and 5 HT2A 英语 5 HT2A receptor 38 註釋 编辑 D2sh TAAR1 is a presynaptic heterodimer which involves the relocation of TAAR1 from the intracellular space to D2sh at the plasma membrane increased D2sh agonist binding affinity and signal transduction through the calcium PKC NFAT 英语 NFAT pathway and G protein independent PKB GSK3 英语 GSK3 pathway 34 35 參考文獻 编辑 對dopamine receptor D2起作用的藥物 在維基數據上查看 編輯參考 2 0 2 1 2 2 GRCh38 Ensembl release 89 ENSG00000149295 Ensembl May 2017 3 0 3 1 3 2 GRCm38 Ensembl release 89 ENSMUSG00000032259 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Madras BK History of the discovery of the antipsychotic dopamine D2 receptor a basis for the dopamine hypothesis of schizophrenia Journal of the History of the Neurosciences 2013 22 1 62 78 PMID 23323533 doi 10 1080 0964704X 2012 678199 Usiello A Baik JH Rouge Pont F Picetti R Dierich A LeMeur M Piazza PV Borrelli E Distinct functions of the two isoforms of dopamine D2 receptors Nature Nov 2000 408 6809 199 203 PMID 11089973 doi 10 1038 35041572 Saab BJ Georgiou J Nath A Lee FJ Wang M Michalon A Liu F Mansuy IM Roder JC NCS 1 in the dentate gyrus promotes exploration synaptic plasticity and rapid acquisition of spatial memory Neuron Sep 2009 63 5 643 56 PMID 19755107 doi 10 1016 j neuron 2009 08 014 Wiemerslage L Schultz BJ Ganguly A Lee D Selective degeneration of dopaminergic neurons by MPP and its rescue by D2 autoreceptors in Drosophila primary culture Journal of Neurochemistry Aug 2013 126 4 529 40 PMID 23452092 doi 10 1111 jnc 12228 Entrez Gene DRD2 dopamine receptor D2 原始内容存档于2010 03 07 11 0 11 1 11 2 Beaulieu JM Gainetdinov RR The physiology signaling and pharmacology of dopamine receptors Pharmacological Reviews Mar 2011 63 1 182 217 PMID 21303898 doi 10 1124 pr 110 002642 UniProt P14416 Duan J Wainwright MS Comeron JM Saitou N Sanders AR Gelernter J Gejman PV Synonymous mutations in the human dopamine receptor D2 DRD2 affect mRNA stability and synthesis of the receptor Human Molecular Genetics Feb 2003 12 3 205 16 PMID 12554675 doi 10 1093 hmg ddg055 Arinami T Gao M Hamaguchi H Toru M A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia Human Molecular Genetics Apr 1997 6 4 577 82 PMID 9097961 doi 10 1093 hmg 6 4 577 Glatt SJ Faraone SV Tsuang MT DRD2 141C insertion deletion polymorphism is not associated with schizophrenia results of a meta analysis American Journal of Medical Genetics Part B Neuropsychiatric Genetics Jul 2004 128B 1 21 3 PMID 15211624 doi 10 1002 ajmg b 30007 Lucht M Rosskopf D Comment on Genetically determined differences in learning from errors Science Jul 2008 321 5886 200 author reply 200 PMID 18621654 doi 10 1126 science 1155372 Wang J Liu ZL Chen B Association study of dopamine D2 D3 receptor gene polymorphisms with motor fluctuations in PD Neurology Jun 2001 56 12 1757 9 PMID 11425949 doi 10 1212 WNL 56 12 1757 Wang J Zhao C Chen B Liu ZL Polymorphisms of dopamine receptor and transporter genes and hallucinations in Parkinson s disease Neuroscience Letters Jan 2004 355 3 193 6 PMID 14732464 doi 10 1016 j neulet 2003 11 006 Clinical Pharmacology for Abilify RxList com 2010 01 21 2010 01 21 原始内容存档于2010 01 18 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 The identification of a selective dopamine D2 partial agonist D3 antagonist displaying high levels of brain exposure Bioorganic amp Medicinal Chemistry Letters Mar 2010 20 6 2013 6 PMID 20153647 doi 10 1016 j bmcl 2010 01 090 Giacomelli S Palmery M Romanelli L Cheng CY Silvestrini B Lysergic acid diethylamide LSD is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine mediated prolactin secretion in lactotrophs in vitro Life Sciences 1998 63 3 215 22 PMID 9698051 doi 10 1016 S0024 3205 98 00262 8 Wang GJ Volkow ND Thanos PK Fowler JS Similarity between obesity and drug addiction as assessed by neurofunctional imaging a concept review Journal of Addictive Diseases 2004 23 3 39 53 PMID 15256343 doi 10 1300 J069v23n03 04 Huang R Griffin SA Taylor M Vangveravong S Mach RH Dillon GH Luedtke RR The effect of SV 293 a D2 dopamine receptor selective antagonist on D2 receptor mediated GIRK channel activation and adenylyl cyclase inhibition Pharmacology 2013 92 1 2 84 9 PMID 23942137 doi 10 1159 000351971 Agnati LF Ferre S Genedani S Leo G Guidolin D Filaferro M Carriba P Casado V Lluis C Franco R Woods AS Fuxe K Allosteric modulation of dopamine D2 receptors by homocysteine Journal of Proteome Research Nov 2006 5 11 3077 83 PMID 17081059 doi 10 1021 pr0601382 Beyaert MG Daya RP Dyck BA Johnson RL Mishra RK PAOPA a potent dopamine D2 receptor allosteric modulator prevents and reverses behavioral and biochemical abnormalities in an amphetamine sensitized preclinical animal model of schizophrenia European Neuropsychopharmacology Mar 2013 23 3 253 62 PMID 22658400 doi 10 1016 j euroneuro 2012 04 010 Lane JR Donthamsetti P Shonberg J Draper Joyce CJ Dentry S Michino M Shi L Lopez L Scammells PJ Capuano B Sexton PM Javitch JA Christopoulos A A new mechanism of allostery in a G protein coupled receptor dimer Nature Chemical Biology Sep 2014 10 9 745 52 PMID 25108820 doi 10 1038 nchembio 1593 Maggio R Scarselli M Capannolo M Millan MJ Novel dimensions of D3 receptor function Focus on heterodimerisation transactivation and allosteric modulation European Neuropsychopharmacology Sep 2015 25 9 1470 9 PMID 25453482 doi 10 1016 j euroneuro 2014 09 016 Silvano E Millan MJ Mannoury la Cour C Han Y Duan L Griffin SA Luedtke RR Aloisi G Rossi M Zazzeroni F Javitch JA Maggio R The tetrahydroisoquinoline derivative SB269 652 is an allosteric antagonist at dopamine D3 and D2 receptors Molecular Pharmacology Nov 2010 78 5 925 34 PMC 2981362 PMID 20702763 doi 10 1124 mol 110 065755 Moller D Kling RC Skultety M Leuner K Hubner H Gmeiner P Functionally selective dopamine D D receptor partial agonists Journal of Medicinal Chemistry Jun 2014 57 11 4861 75 PMID 24831693 doi 10 1021 jm5004039 Binda AV Kabbani N Lin R Levenson R D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4 1N Molecular Pharmacology Sep 2002 62 3 507 13 PMID 12181426 doi 10 1124 mol 62 3 507 Smith FD Oxford GS Milgram SL Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin a protein phosphatase 1 interacting protein The Journal of Biological Chemistry Jul 1999 274 28 19894 900 PMID 10391935 doi 10 1074 jbc 274 28 19894 Kabbani N Negyessy L Lin R Goldman Rakic P Levenson R Interaction with neuronal calcium sensor NCS 1 mediates desensitization of the D2 dopamine receptor The Journal of Neuroscience Oct 2002 22 19 8476 86 PMID 12351722 Beaulieu JM Espinoza S Gainetdinov RR Dopamine receptors IUPHAR Review 13 British Journal of Pharmacology Jan 2015 172 1 1 23 PMC 4280963 PMID 25671228 doi 10 1111 bph 12906 Grandy DK Miller GM Li JX TAARgeting Addiction The Alamo Bears Witness to Another Revolution An Overview of the Plenary Symposium of the 2015 Behavior Biology and Chemistry Conference Drug Alcohol Depend February 2016 159 9 16 PMID 26644139 doi 10 1016 j drugalcdep 2015 11 014 This original observation of TAAR1 and DA D2R interaction has subsequently been confirmed and expanded upon with observations that both receptors can heterodimerize with each other under certain conditions Additional DA D2R TAAR1 interactions with functional consequences are revealed by the results of experiments demonstrating that in addition to the cAMP PKA pathway Panas et al 2012 stimulation of TAAR1 mediated signaling is linked to activation of the Ca PKC NFAT pathway Panas et al 2012 and the DA D2R coupled G protein independent AKT GSK3 signaling pathway Espinoza et al 2015 Harmeier et al 2015 such that concurrent TAAR1 and DA DR2R activation could result in diminished signaling in one pathway e g cAMP PKA but retention of signaling through another e g Ca PKC NFA Harmeier A Obermueller S Meyer CA Revel FG Buchy D Chaboz S Dernick G Wettstein JG Iglesias A Rolink A Bettler B Hoener MC Trace amine associated receptor 1 activation silences GSK3b signaling of TAAR1 and D2R heteromers Eur Neuropsychopharmacol 2015 25 11 2049 61 PMID 26372541 doi 10 1016 j euroneuro 2015 08 011 Interaction of TAAR1 with D2R altered the subcellular localization of TAAR1 and increased D2R agonist binding affinity Maggio R Millan MJ Dopamine D2 D3 receptor heteromers pharmacological properties and therapeutic significance Current Opinion in Pharmacology Feb 2010 10 1 100 7 PMID 19896900 doi 10 1016 j coph 2009 10 001 Hasbi A O Dowd BF George SR Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms Current Opinion in Pharmacology Feb 2010 10 1 93 9 PMC 2818238 PMID 19897420 doi 10 1016 j coph 2009 09 011 Albizu L Holloway T Gonzalez Maeso J Sealfon SC Functional crosstalk and heteromerization of serotonin 5 HT2A and dopamine D2 receptors Neuropharmacology Sep 2011 61 4 770 7 PMC 3556730 PMID 21645528 doi 10 1016 j neuropharm 2011 05 023 外部連結 编辑醫學主題詞表 MeSH Receptors Dopamine D2 Pappas Stephanie Study Genes Influence Who Your Friends Are Imaginova Corp LiveScience 20 January 2011 多巴胺受體D2引用了美国国家医学图书馆提供的資料 这些資料属于公共领域 Template Dopaminergics 取自 https zh wikipedia org w index php title 多巴胺受體D2 amp oldid 74894134, 维基百科，wiki，书籍，书籍，图书馆，

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