多巴胺受體D₂

多巴胺受体D2
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	6CM4
识别号
别名	DRD2；, D2DR, D2R, dopamine receptor D2
外部ID	OMIM：126450 MGI：94924 HomoloGene：22561 GeneCards：DRD2
相关疾病
	重性抑郁障碍
为以下药物的标靶
	remoxipride
	benzquinamide、LP-12、LP-211、LP-44、罗匹尼罗、罗替戈汀、维拉佐酮、7-hydroxy-2-(di-N-propylamino)tetralin、溴隐亭、多巴胺、培高利特、普拉克索、quinelorane、quinpirole、苏马尼罗、阿朴吗啡、阿立哌唑、brexpiprazole、过乳降、麦角乙脲、吡贝地尔、roxindole、特麦角脲、氨磺必利、布南色林、布他拉莫、氯丙嗪、氯氮平、多潘立酮、eticlopride、三氟噻吨、氟奋乃静、氟哌啶醇、L-741,626、洛沙平、mesoridazine、那法道曲、奥氮平、perospirone、奋乃静、匹莫齐特、pipotiazine、普乐明、丙嗪、喹硫平、raclopride、利培酮、sertindole、舒必利、levosulpiride、三氟拉嗪、齐拉西酮、zotepine
基因位置（人类）
染色体	11号染色体
终止	113,475,691 bp
基因位置（小鼠）
染色体	小鼠9号染色体
终止	49,319,477 bp
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本体
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;
细胞组分	• cytoplasmic vesicle; • sperm flagellum; • endocytic vesicle; • 顶体; • 树突棘; • synaptic vesicle membrane; • 细胞本体; • 细胞膜; • 树突; • ciliary membrane; • 神经末梢; • integral component of membrane; • 突触后致密物质; • 膜; • lateral plasma membrane; • 轴突; • 胞内; • 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;
生物学过程	• 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; • 联想型学习; • 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; • 讯息传递; • 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; • 进食行为; • 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; • 蠕动; • 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; • 前脉冲抑制; • 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; • 色素沉着; • 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; • 惊跳反射; • 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; • 兴奋性动作电位; • 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 exocytosis;
	Sources:Amigo / QuickGO
直系同源
	1813
	13489
	ENSG00000149295
	ENSMUSG00000032259
	P14416
	P61168
	NM_016574; NM_000795
	NM_010077
	NP_000786; NP_057658; NP_000786.1
	NP_034207
	维基数据
查看/编辑人类	查看/编辑小鼠

多巴胺受体D₂（Dopamine receptor D₂，简称D2R），为转译自 DRD2 基因的一种多巴胺受体蛋白。D2R最早于1975年为Philip Seeman（英语：Philip Seeman）所发现，并将其命名为“抗精神疾患性多巴胺受体”（antipsychotic dopamine receptor）^[8]。D2R为所有抗精神病药物的作用标的。

功能

D2R属于一种多巴胺受体，并会与G_i结合。G_i为G蛋白偶联受体的一种亚型，会抑制腺苷酸环化酶的活性^[9]。

在小鼠模式中，齿状回的neuronal calcium sensor-1（英语：neuronal calcium sensor-1）（NCS-1）会影响D2R在细胞膜的表现量。这项机制会影响突触可塑性及记忆形成^[10]。

在苍蝇模式中，多巴胺性神经元上的D2R自体受器（英语：autoreceptor）能避免神经元死亡，进而引发类帕金森氏症的症状^[11]。

同型体

此基因的选择性剪接产生三种不同编码亚型的转录变体。^[12]

长形式（D2Lh）具有"规范"的序列，并作为经典突触后蛋白发挥作用。^[13]短形式（D2Sh）在突触前作为调节突触间隙中多巴胺水平的自身受体发挥作用。^[13]D2Sh受体激动时抑制多巴胺释放，拮抗时增加多巴胺释放。^[13]第三种D2（更长）的形式不同于270V被VVQ取代的规范序列。^[14]

基因组

等位基因变异：

A-241G
C132T、G423A、T765C、C939T、C957T（英语：C957T），以及G1101A^[15]
Cys311Ser
-141C insertion/deletion^[16]The polymorphisms have been investigated with respect to association with schizophrenia.^[17]

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.^[18]DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinson's disease.^[19]^[20]

配体

大多数较老的抗精神病药如氯丙嗪或氟哌啶醇是多巴胺D₂受体的非选择性拮抗剂，最多仅对"D₂样家族"受体具有选择性，因此与D₂、D₃、D₄以及许多其他受体都可以结合，例如血清素和组胺受体，导致一系列副作用使得它们不适合科学研究。类似，用于治疗帕金森病的较旧的多巴胺激动剂例如溴隐亭和卡麦角林，对一种多巴胺受体的选择性较差，尽管这些药物中大多数确实能起到D₂激动剂的作用，但它们也会影响其他多巴胺受体，亚型也是。现今有几种选择性D₂配体 (生物化学)可以使用，并且随着进一步的研究，这个数字可能会增加。

受体致活剂

溴隐亭（Bromocriptine）：完全受体致活剂
Cabergoline（英语：Cabergoline）（Caberl）
N,N-Propyldihydrexidine：D₁/D₅受体制活剂dihydrexidine（英语：dihydrexidine）的类似物，对节后神经元的D2R亲和性比节前神经元的D₂自体受器（英语：autoreceptor）高。
Piribedil：同时也是 D₃ 受体致活剂及肾上腺素α₂受体拮抗剂（英语：α2-adrenergic receptor）
Pramipexole（英语：Pramipexole）：同时也是D₃、D₄受体致活剂
Quinelorane（英语：Quinelorane）：affinity for D₂ > D₃
Quinpirole（英语：Quinpirole）：同时也是D₃受体致活剂
Ropinirole：完全受体致活剂
Sumanirole（英语：Sumanirole）：高选择性完全受体致活剂
Talipexole（英语：Talipexole）：对D₂的亲和性高于其他的多巴胺受体，但同时也是肾上腺素α₂受体制活剂及5-HT₃受体拮抗剂。

部分受体致活剂

Aplindore（英语：Aplindore）
阿立哌唑（Aripiprazole，在美国合法）^[21]
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 ^[22]
氯胺酮（Ketamine，同时也为NMDA受体拮抗剂）
LSD – in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs.^[23]LSD is also a 5-HT_2A agonist.
莫达非尼（Modafinil）
Roxindole（英语：Roxindole） (only at the D₂ autoreceptors)
OSU-6162（英语：OSU-6162）：亦为5-HT_2A部分受体致活剂，acts as "dopamine stabilizer"
Salvinorin A（英语：Salvinorin A）：亦为κ-鸦片类受体致活剂（英语：Κ-opioid receptor）。

受体拮抗剂

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^[24]
Typical antipsychotics（英语：Typical antipsychotics）
SV 293^[25]
Yohimbine

D₂sh selective (presynaptic autoreceptors)

氨磺必利 (low doses)
UH-232

异位调控因子

Homocysteine – 负向异位调控因子（英语：allosteric modulator）^[26]
PAOPA^[27]
SB-269,652 ^[28]^[29]^[30]

Functionally selective ligands

参见参考文献^[31]。

Protein–protein interactions

多巴胺受体 D₂ 已被证明与EPB41L1（英语：EPB41L1）、^[32]PPP1R9B（英语：PPP1R9B）^[33] 和 NCS-1（英语：NCS-1）相互作用。^[34]

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:^[35]

D₁–D₂ dopamine receptor heteromer（英语：D1–D2 dopamine receptor heteromer）
D₂–adenosine A_2A
D₂–ghrelin receptor（英语：ghrelin receptor）
D_2sh–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）,^[38]DRD₅（英语：Dopamine receptor D5）,^[39]and 5-HT_2A（英语：5-HT2A receptor）.^[40]

注释

^ 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 pathway and G-protein independent PKB–GSK3（英语：GSK3） pathway.^[36]^[37]

参考文献

^ 與多巴胺受體D2相關的疾病；在維基數據上查看/編輯參考.
^ 對Dopamine receptor D2, isoform CRA_c起作用的藥物；在維基數據上查看/編輯參考.
^ 對Dopamine receptor D2起作用的藥物；在維基數據上查看/編輯參考.
^ ^4.0 ^4.1 ^4.2 GRCh38: Ensembl release 89: ENSG00000149295 - Ensembl, May 2017
^ ^5.0 ^5.1 ^5.2 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, 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.
^ 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）.
^ ^13.0 ^13.1 ^13.2 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 & 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, 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.
^ 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, 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.
^ 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.
^ 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.
^ 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 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.
^ 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, 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.

外部链接

医学主题词表（MeSH）：Receptors,+Dopamine+D2
Pappas, Stephanie. Study: Genes Influence Who Your Friends Are. Imaginova Corp. LiveScience. [20 January 2011].

多巴胺受体D2引用了美国国家医学图书馆提供的资料，这些资料属于公共领域。

Template:Dopaminergics

[38] 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 pathway and G-protein independent PKB–GSK3（英语：GSK3） pathway.^[36]^[37]

[1] 與多巴胺受體D2相關的疾病；在維基數據上查看/編輯參考.

[2] 對Dopamine receptor D2, isoform CRA_c起作用的藥物；在維基數據上查看/編輯參考.

[3] 對Dopamine receptor D2起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-4] 4.0 ^4.1 ^4.2 GRCh38: Ensembl release 89: ENSG00000149295 - Ensembl, May 2017

[refGRCm38Ensembl-5] 5.0 ^5.1 ^5.2 GRCm38: Ensembl release 89: ENSMUSG00000032259 - Ensembl, May 2017

[6] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[7] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[8] 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.

[pmid11089973-9] 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.

[pmid19755107-10] 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.

[pmid23452092-11] 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-12] Entrez Gene: DRD2 dopamine receptor D2. （原始内容存档于2010-03-07）.

[D2_Long_and_short-13] 13.0 ^13.1 ^13.2 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-14] UniProt P14416

[pmid12554675-15] 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.

[pmid9097961-16] 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.

[pmid15211624-17] 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.

[pmid18621654-18] 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.

[pmid11425949-19] 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_Z._2004-20] 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.

[Rxlist_-_Abilify-21] Clinical Pharmacology for Abilify. RxList.com. 2010-01-21 [2010-01-21]. （原始内容存档于2010-01-18）.

[pmid20153647-22] 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.

[pmid9698051-23] 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.

[pmid15256343-24] 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.

[25] 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.

[26] 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.

[27] 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.

[pmid25108820-28] 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.

[pmid25453482-29] 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.

[30] 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.

[pmid24831693-31] 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.

[pmid12181426-32] 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.

[pmid10391935-33] 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.

[pmid12351722-34] 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.

[DA_receptor_heterodimers-35] 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.

[Miller+Grandy_2016-36] 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)

[TAAR1-D2sh-37] 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.

[39] 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.

[40] 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.

[41] 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.

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