Dopamine Receptors: A Classification
Dopamine Receptors: A Classification
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多巴胺受体：分类
DOI：
10.1097/00004714-198210000-00009
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发表时间：
1982
影响因子：
2.9
通讯作者：
S. Leff
中科院分区：
文献类型：
--
作者：
I. Creese;S. Leff
生物化学和药理学研究已经确定了至少两类多巴胺受体。D-1受体介导的腺苷酸环化酶活性的刺激微摩尔浓度的多巴胺，它们拮抗吩噻嗪和噻吨与纳摩尔效力和丁酰苯与微摩尔效力。D-2受体介导腺苷酸环化酶活性的抑制，或者它们与该酶不相关。这些受体被纳摩尔浓度的多巴胺激动剂刺激，并且它们被纳摩尔浓度的丁酰苯、吩噻嗪和噻吨拮抗。D-1受体由[3 H]氟哌噻吨标记，在纹状体中，它们几乎完全存在于内在神经元上。它们的生理功能，以及它们在介导多巴胺激动剂刺激行为中的作用尚不清楚。D-2受体由3 H-丁酰苯、3 H-激动剂和[3 H]氟哌噻吨标记。激动剂/3 H-丁酰苯酮竞争实验在脑垂体和纹状体中产生Hill斜率<<1。这些数据解释了一个模型，其中D-2受体表现出高亲和力和低亲和力状态的激动剂。鸟嘌呤核苷酸将这种平衡向低亲和力状态移动，并且它们可能在调节多巴胺激动剂刺激的生理反应中起重要作用。D-2受体的激动剂刺激与抗帕金森病活性相关，而该受体的拮抗剂亲和力与抗精神病效力相关。在纹状体中，D-2受体至少与内在神经元和皮质纹状体传入终末相关。在纹状体中发现了一个称为D-3的额外结合位点。该位点被纳摩尔浓度的3 H-激动剂标记，但对丁酰苯具有微摩尔亲和力。这些位点可能代表3 H-激动剂结合突触前自身受体和/或结合突触后D-1受体的高激动剂亲和力状态。
Biochemical and pharmacological studies have identified at least two classes of dopamine receptors. D-1 receptors mediate the stimulation of adenylate cyclase activity by micromolar concentrations of dopamine, and they are antagonized by phenothiazines and thioxanthenes with nanomolar potencies and by butyrophenones with micromolar potencies. D-2 receptors mediate either the inhibition of adenylate cyclase activity or they are un-associated with this enzyme. These receptors are stimulated by nanomolar concentrations of dopamine agonists, and they are antagonized by nanomolar concentrations of butyrophenones, phenothiazines, and thioxanthenes. D-1 receptors are labeled by [3H]flupentixol, and in the striatum they are found almost entirely on intrinsic neurons. Their physiological function, as well as their role in mediating dopamine agonist-stimulated behaviors, is unclear. D-2 receptors are labeled by 3H-butyrophenones, 3H-agonists, and [3H]flupentixol. Agonist/3H-butyrophenone competition experiments produce Hill slopes <<1 in both the pituitary and striatum. These data are explained by a model whereby D-2 receptors show both a high affinity and low affinity state for agonists. Guanine nucleotides shift this equilibrium toward the low affinity state, and they likely play an important role in the regulation of dopamine agonist-stimulated physiological responses. Agonist stimulation of D-2 receptors is correlated with antiparkinsonian activity, and antagonist affinities at this receptor correlate with antipsychotic potency. In the striatum D-2 receptors are associated with at least intrinsic neurons and corticostriate afferent terminals. An additional binding site termed D-3 has been identified in striatum. This site is labeled by nanomolar concentrations of 3H-agonists but has micromolar affinity for butyrophenones. These sites may represent both 3H-agonist binding to presynaptic autoreceptors and/or binding to a high agonist affinity state of postsynaptic D-1 receptors.