维基百科中的医学内容
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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。
Quick Facts 多巴胺受体D2, 已知的结构 ...
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D2R属于一种多巴胺受体，并会与Gi结合。Gi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（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自体受器能避免神经元死亡，进而引发类帕金森氏症的症状[11]。
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]
等位基因变异：
- A-241G
- C132T、G423A、T765C、C939T、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 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]
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。
- 溴隐亭（Bromocriptine）：完全受体致活剂
- Cabergoline（Caberl）
- N,N-Propyldihydrexidine：D1/D5受体制活剂dihydrexidine的类似物，对节后神经元的D2R亲和性比节前神经元的D2自体受器高。
- Piribedil：同时也是 D3 受体致活剂及肾上腺素α2受体拮抗剂
- Pramipexole：同时也是D3、D4受体致活剂
- Quinelorane：affinity for D2 > D3
- Quinpirole：同时也是D3受体致活剂
- Ropinirole：完全受体致活剂
- Sumanirole：高选择性完全受体致活剂
- 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。
- Aplindore
- 阿立哌唑（Aripiprazole，在美国合法）[21]
- Brexpiprazole/OPC-34712
- Cariprazine
- RP5063
- 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-HT2A agonist.
- 莫达非尼（Modafinil）
- Roxindole (only at the D2 autoreceptors)
- OSU-6162：亦为5-HT2A部分受体致活剂，acts as "dopamine stabilizer"
- Salvinorin A：亦为κ-鸦片类受体致活剂。
- Atypical antipsychotics
- Desmethoxyfallypride
- Domperidone – D2 and D3 antagonist; does not cross the blood-brain barrier
- Eticlopride
- Fallypride
- Hydroxyzine (Vistaril, Atarax)
- Itopride
- L-741,626 – highly selective D2 antagonist
- C11 Raclopride radiolabled – commonly employed in positron emission tomography studies[24]
- Typical antipsychotics
- SV 293[25]
- Yohimbine
- D2sh selective (presynaptic autoreceptors)
多巴胺受体 D2 已被证明与EPB41L1、[32]PPP1R9B[33] 和 NCS-1 相互作用。[34]
The D2 receptor forms receptor heterodimers in vivo (in living animals) with other G protein-coupled receptors; these include:[35]
The D2 receptor has been shown to form hetorodimers in vitro (and possibly in vivo) with DRD3,[38]DRD5,[39]and 5-HT2A.[40]
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. 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. 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)
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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。
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