D1/D2 Dopamine Receptor Interactions in Basal Ganglia Functions
D1/D2 Dopamine Receptor Interactions in Basal Ganglia Functions
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D1/D2 多巴胺受体在基底神经节功能中的相互作用
DOI：
10.1007/978-1-4757-2635-0_7
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发表时间：
1997
影响因子：
20.1
通讯作者：
G. Lahoste
中科院分区：
文献类型：
--
作者：
J. Marshall;D. N. Ruskin;G. Lahoste
Kebabian和卡尔内（1）在1979年将多巴胺（DA）受体分为两种亚型（DI和D2），这是基于与腺苷酸环化酶的不同连接以及不同的药理学特征。在提出这种分类的时候，有几条证据表明，D2受体在多巴胺介导的行为功能中发挥作用，而D1受体则没有。例如，已知体内给予D2拮抗剂可阻断安非他明或可卡因等药物的运动兴奋剂和奖励特性（3，4）。给予D2激动剂可产生自发活动和刻板运动（5）。此外，一系列抗精神病药物的临床效力被发现与它们对D2受体的亲和力相关（6，7）。回想起来，很明显，认识到D1受体激动对基底神经节内多巴胺作用的重要性的缓慢有两个原因。首先，缺乏DI受体特异性的药理学试剂，阻碍了研究人员分离这种受体的功能。其次，正如我们现在所认识到的，D1受体的影响可能很难检测到。D1和D2受体之间的相互作用被深刻地改变了黑质纹状体损伤，并且，在完整的动物，他们的解释取决于欣赏内源性DA在提供强直DI激动作用所发挥的作用。
The classification by Kebabian and Calne (1) in 1979 of dopamine (DA) receptors into two subtypes (DI and D2) was based on differential linkages to adenylate cyclase as well as on distinct pharmacological profiles. At the time that this classification was proposed, several lines of evidence pointed to a role for D2, but not D1, receptors in the behavioral functions mediated by dopamine.* For instance, in vivo administration of D2 antagonists was known to block the motor stimulant and rewarding properties of agents such as amphetamine or cocaine (3, 4). Administration of D2 agonists produces locomotor activity and stereotyped movements (5). Also, the clinical potencies ofa series of antipsychotic drugs were found to correlate with their affinities for D2 receptors (6, 7). In retrospect, it seems clear that the slowness to recognize the importance of D1 receptor agonism to dopamine’s effects within basal ganglia occurred for two reasons. First, a lack of pharmacological agents specific for DI receptors precluded researchers from isolating the functions of this receptor. Second, as we now appreciate, the influences of D1 receptors can be subtle to detect. The interactions between D1 and D2 receptors are profoundly changed by nigrostriatal injury; and, in intact animals, their interpretation depends on an appreciation of the role played by endogenous DA in providing tonic DI agonism.
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期刊：
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期刊：
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