多巴胺受體D₂

多巴胺受體D2
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	6CM4
識別號
別名	DRD2；, D2DR, D2R, dopamine receptor D2
外部ID	OMIM：126450 MGI：94924 HomoloGene：22561 GeneCards：DRD2
相關疾病
	重性抑鬱障礙
為以下藥物的標靶
	remoxipride
	benzquinamide、LP-12、LP-211、LP-44、羅匹尼羅、羅替戈汀、維拉佐酮、7-hydroxy-2-(di-N-propylamino)tetralin、溴隱亭、多巴胺、培高利特、普拉克索、quinelorane、quinpirole、蘇馬尼羅、阿樸嗎啡、阿立哌唑、brexpiprazole、過乳降、麥角乙脲、吡貝地爾、roxindole、特麥角脲、氨磺必利、布南色林、布他拉莫、氯丙嗪、氯氮平、多潘立酮、eticlopride、三氟噻噸、氟奮乃靜、氟哌啶醇、L-741,626、洛沙平、mesoridazine、那法道曲、奧氮平、perospirone、奮乃靜、匹莫齊特、pipotiazine、普樂明、丙嗪、喹硫平、raclopride、利培酮、sertindole、舒必利、levosulpiride、三氟拉嗪、齊拉西酮、zotepine
基因位置（人類）
染色體	11號染色體
終止	113,475,691 bp
基因位置（小鼠）
染色體	小鼠9號染色體
終止	49,319,477 bp
RNA表現模式
	; ; ; ;
	查閱更多表現資料
基因本體
分子功能	• protein homodimerization activity; • potassium channel regulator activity; • dopamine neurotransmitter receptor activity, coupled via Gi/Go; • 相同蛋白質結合; • dopamine neurotransmitter receptor activity; • G protein-coupled receptor activity; • 血漿蛋白結合; • 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; • 頂體; • 樹突棘; • synaptic vesicle membrane; • 細胞本體; • 細胞膜; • 樹突; • ciliary membrane; • 神經末梢; • integral component of membrane; • 突觸後緻密物質; • 膜; • lateral plasma membrane; • 軸突; • 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; • 個人儀容; • negative regulation of protein kinase B signaling; • 聯想型學習; • 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信號通路; • 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; • 進食行為; • 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; • 前脈衝抑制; • response to morphine; • response to iron ion; • positive regulation of ERK1 and ERK2 cascade; • 長期記憶; • 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; • 色素沉著; • 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 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
	維基資料
檢視/編輯人類	檢視/編輯小鼠

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（英語：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）^[8]。D2R為所有抗精神病藥物的作用標的。

功能

D2R屬於一種多巴胺受體，並會與G_i結合。G_i為G蛋白偶聯受體的一種亞型，會抑制腺苷酸環化酶的活性^[9]。

在小鼠模式中，齒狀回的neuronal calcium sensor-1（英語：neuronal calcium sensor-1）（NCS-1）會影響D2R在細胞膜的表現量。這項機制會影響突觸可塑性及記憶形成^[10]。

在蒼蠅模式中，多巴胺性神經元上的D2R自體受器（英語：autoreceptor）能避免神經元死亡，進而引發類帕金森氏症的症狀^[11]。

同型體

此基因的選擇性剪接產生三種不同編碼亞型的轉錄變體。^[12]

長形式（D2Lh）具有"規範"的序列，並作為經典突觸後蛋白發揮作用。^[13]短形式（D2Sh）在突觸前作為調節突觸間隙中多巴胺水平的自身受體發揮作用。^[13]D2Sh受體激動時抑制多巴胺釋放，拮抗時增加多巴胺釋放。^[13]第三種D2（更長）的形式不同於270V被VVQ取代的規範序列。^[14]

基因組

等位基因變異：

A-241G
C132T、G423A、T765C、C939T、C957T（英語：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（英語：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]

配體

大多數較老的抗精神病藥如氯丙嗪或氟哌啶醇是多巴胺D₂受體的非選擇性拮抗劑，最多僅對"D₂樣家族"受體具有選擇性，因此與D₂、D₃、D₄以及許多其他受體都可以結合，例如血清素和組織胺受體，導致一系列副作用使得它們不適合科學研究。類似，用於治療巴金森氏症的較舊的多巴胺促效劑例如溴隱亭和卡麥角林，對一種多巴胺受體的選擇性較差，儘管這些藥物中大多數確實能起到D₂促效劑的作用，但它們也會影響其他多巴胺受體，亞型也是。現今有幾種選擇性D₂配體 (生物化學)可以使用，並且隨著進一步的研究，這個數字可能會增加。

受體致活劑

溴隱亭（Bromocriptine）：完全受體致活劑
Cabergoline（英語：Cabergoline）（Caberl）
N,N-Propyldihydrexidine：D₁/D₅受體制活劑dihydrexidine（英語：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（英語：autoreceptor）高。
Piribedil：同時也是 D₃ 受體致活劑及腎上腺素α₂受體拮抗劑（英語：α2-adrenergic receptor）
Pramipexole（英語：Pramipexole）：同時也是D₃、D₄受體致活劑
Quinelorane（英語：Quinelorane）：affinity for D₂ > D₃
Quinpirole（英語：Quinpirole）：同時也是D₃受體致活劑
Ropinirole：完全受體致活劑
Sumanirole（英語：Sumanirole）：高選擇性完全受體致活劑
Talipexole（英語：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（英語：Aplindore）
阿立哌唑（Aripiprazole，在美國合法）^[21]
Brexpiprazole（英語：Brexpiprazole）/OPC-34712（英語：OPC-34712）
Cariprazine（英語：Cariprazine）
RP5063（英語：RP5063）
GSK-789,472（英語：GSK-789,472） – Also D₃ antagonist, with good selectivity over other receptors ^[22]
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.^[23]LSD is also a 5-HT_2A agonist.
莫達非尼（Modafinil）
Roxindole（英語：Roxindole） (only at the D₂ autoreceptors)
OSU-6162（英語：OSU-6162）：亦為5-HT_2A部分受體致活劑，acts as "dopamine stabilizer"
Salvinorin A（英語：Salvinorin A）：亦為κ-鴉片類受體致活劑（英語：Κ-opioid receptor）。

受體拮抗劑

Atypical antipsychotics（英語：Atypical antipsychotics）
Desmethoxyfallypride（英語：Desmethoxyfallypride）
Domperidone – D₂ and D₃ antagonist; does not cross the blood-brain barrier
Eticlopride（英語：Eticlopride）
Fallypride（英語：Fallypride）
Hydroxyzine (Vistaril, Atarax)
Itopride（英語：Itopride）
L-741,626（英語：L-741,626） – highly selective D₂ antagonist
C¹¹ Raclopride（英語：Raclopride） radiolabled – commonly employed in positron emission tomography studies^[24]
Typical antipsychotics（英語：Typical antipsychotics）
SV 293^[25]
Yohimbine

D₂sh selective (presynaptic autoreceptors)

氨磺必利 (low doses)
UH-232

異位調控因子

Homocysteine – 負向異位調控因子（英語：allosteric modulator）^[26]
PAOPA^[27]
SB-269,652 ^[28]^[29]^[30]

Functionally selective ligands

參見參考文獻^[31]。

Protein–protein interactions

多巴胺受體 D₂ 已被證明與EPB41L1（英語：EPB41L1）、^[32]PPP1R9B（英語：PPP1R9B）^[33] 和 NCS-1（英語：NCS-1）相互作用。^[34]

Receptor oligomers

The D₂ receptor forms receptor heterodimers（英語：GPCR oligomer） in vivo (in living animals) with other G protein-coupled receptors; these include:^[35]

D₁–D₂ dopamine receptor heteromer（英語：D1–D2 dopamine receptor heteromer）
D₂–adenosine A_2A
D₂–ghrelin receptor（英語：ghrelin receptor）
D_2sh–TAAR1（英語：TAAR1）^{[note 1]}

The D₂ receptor has been shown to form hetorodimers in vitro (and possibly in vivo) with DRD₃（英語：Dopamine D3 receptor）,^[38]DRD₅（英語：Dopamine receptor D5）,^[39]and 5-HT_2A（英語：5-HT2A receptor）.^[40]

註釋

^ 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（英語：GSK3） pathway.^[36]^[37]

參考文獻

^ 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.
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^ Entrez Gene: DRD2 dopamine receptor D2. （原始內容存檔於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]. （原始內容存檔於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.
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^ 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引用了美國國家醫學圖書館提供的資料，這些資料屬於公共領域。

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（英語：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

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[uniprot-14] UniProt P14416

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[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.

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[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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