Prazosin: differential affinities for two populations of α-noradrenergic receptor binding sites
Prazosin: differential affinities for two populations of α-noradrenergic receptor binding sites
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哌唑嗪：两组 α-去甲肾上腺素受体结合位点的不同亲和力
DOI：
10.1016/0014-2999(78)90258-3
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发表时间：
1978
影响因子：
5
通讯作者：
S. Snyder
中科院分区：
文献类型：
--
作者：
D. U'prichard;M. E. Charness;D. Robertson;S. Snyder
哌唑嗪是最近推出的一种抗高血压药物，几乎不会产生直立性低血压和心动过速(Stokes和Oates，1978)。其独特的临床疗效可能涉及对突触后α受体的选择性作用，不同于酚妥拉明和苯氧苯甲胺，后者也阻断位于去甲肾上腺素能神经末梢的α-去甲肾上腺素能自体受体(剑桥等人，1977)。Berthelsen和Pettinger(1977)提出了两个不同的突触后a受体群体，一个具有与突触前自身受体(A2)相同的药理特性，另一个具有与突触后a受体(a~)经典相关的特性。我们描述了两个不同的CNSα-去甲肾上腺素能受体结合部位(参见Peroutka等人，1978年的参考文献)。用~3H-可乐定和~3H-儿茶酚胺标记的受体对激动剂的亲和力最高，而用α-拮抗剂~3H-WB-4101标记的受体对激动剂的亲和力较低，对大多数拮抗剂的亲和力稍高。由于脑室注射6-羟基多巴胺并不耗尽~3H-可乐定或~3H-WB-4101的结合，这两个部位似乎都不涉及自身受体本身。然而，在药物特异性研究中，~3H-WB-4101和~3H~碘核苷结合部位分别类似于a~-和a2-受体和
Prazosin, a recently introduced antihypertensive agent, produces very little orthostatic hypotension and tachycardia (Stokes and Oates, 1978). Its unique clinical efficacy may involve selective actions at postsynaptic a-receptors, unlike phentolamine and phenoxybenzamine which also block a-noradrenergic autoreceptors located on noradrenergic nerve terminals (Cambridge et al., 1977). Blockade of autoreceptors causes overflow of norepinephrine which, by stimulating~-receptors, would produce symptoms such as tachycardia.Berthelsen and Pettinger (1977) have proposed two distinct postsynaptic a-receptor populations, one with the same pharmacological properties as presynaptic autoreceptors (a2), and the other with properties classically associated with postsynaptic a-receptors (a~). We described two distinct CNS a-noradrenergic receptor binding sites (see Peroutka et al., 1978 for refs.). The receptor labaled by 3H-clonidine and 3H-catecholamines has uniquely high affinity for agonists, while the other receptor, labeled by the a-antagonist 3H-WB-4101, has lesser affinity for agonists and somewhat higher affinity for most antagonists. Since intraventricular 6-hydroxydopamine administration does not deplete the binding of 3H-clonidine or 3H-WB-4101, neither of these two sites seems to involve autoreceptors per se. In drug specificity studies, however, 3H-WB-4101 and 3H~ lonidine binding sites resemble a~-and a2-receptors respectively and