Bylund D B, U'Prichard D C
Int Rev Neurobiol. 1983;24:343-431.
Within the short period of 5 years, the availability of a variety of specific radioligands has allowed the resolution of alpha 1- and alpha 2-adrenergic receptor populations in many different tissues and enabled researchers to begin investigations of the mechanisms of regulation and coupling of alpha 1 and alpha 2 receptors to their different cellular effector systems. Binding data have demonstrated that the pharmacological properties of each type of alpha receptor are, in general, similar across tissues and species, although there are some differences in the relative affinities of antagonist drugs. Further attempts to subclassify alpha 1 and alpha 2 receptors may be expected in the future. The historical development of the interpretation of [3H]clonidine binding is of interest in this regard. [3H]Clonidine was proposed to label the "agonist state" of the alpha receptor, and then to label alpha 2 receptors. It is now thought that it labels the agonist state of alpha 2 receptors. Might it actually label a subpopulation of alpha 2 receptors or just the agonist state of that subpopulation? Alpha-1 receptors by and large appear to occur in a single-affinity state with respect to both agonists and antagonists. By comparison, alpha 2 receptors may exist in multiple-affinity states reflecting the ability of the alpha 2 binding site protein to complex to additional membrane proteins which themselves are receptors for the physiological substrates GTP, Na+, Mg2+, and possibly Ca2+-calmodulin. Binding studies have also strongly indicated that alpha 2 receptors in most, if not all, tissues are probably coupled in an inhibitory manner to adenylate cyclase, as has been demonstrated in platelets, adipocytes, and NG 108-15 cells. Clearly the present status of alpha-receptor research has left many questions unresolved. We still have no idea what membrane effector system and associated second messenger is coupled to the alpha 1 receptor. The prevailing belief is that Ca2+ and the membrane Ca2+ channel fulfill these roles. However, others have suggested that phosphoinositide turnover represents the proximal receptor response, and indeed a membrane-bound phospholipase C may play an analogous role to adenylate cyclase for other adrenergic receptors (Putney et al., 1980). There is, however, some evidence that in some situations alpha 1 receptors may directly stimulate adenylate cyclase, and guanine nucleotide modulation of agonist affinities at alpha 1-receptor sites has been reported. The significance of these data and reported modulatory effects of Na+ at alpha 1 receptors (Glossmann and Presek, 1979; Glossmann et al., 1981) is still to be resolved.(ABSTRACT TRUNCATED AT 400 WORDS)
在短短5年时间里，多种特异性放射性配体的出现使得在许多不同组织中分辨α1和α2肾上腺素能受体群体成为可能，并使研究人员能够开始研究α1和α2受体与其不同细胞效应系统的调节和偶联机制。结合数据表明，尽管拮抗剂药物的相对亲和力存在一些差异，但每种类型的α受体的药理学特性在不同组织和物种中总体上是相似的。预计未来会进一步尝试对α1和α2受体进行亚分类。在这方面，[3H]可乐定结合解释的历史发展很有意思。[3H]可乐定最初被认为标记α受体的“激动剂状态”，后来被认为标记α2受体。现在认为它标记α2受体的激动剂状态。它实际上是标记α2受体的一个亚群还是仅仅是该亚群的激动剂状态呢？α1受体在激动剂和拮抗剂方面大体上似乎以单一亲和力状态存在。相比之下，α2受体可能以多种亲和力状态存在，这反映了α2结合位点蛋白与其他膜蛋白结合的能力，而这些膜蛋白本身是生理底物GTP、Na+、Mg2+以及可能的Ca2+-钙调蛋白的受体。结合研究也有力地表明，在大多数（如果不是全部）组织中，α2受体可能以抑制方式与腺苷酸环化酶偶联，这已在血小板（platelets）、脂肪细胞（adipocytes）和NG 108-15细胞中得到证实。显然，α受体研究的现状仍有许多问题未解决。我们仍然不知道与α1受体偶联的膜效应系统和相关的第二信使是什么。普遍的观点是Ca2+和膜Ca2+通道发挥这些作用。然而，其他人认为磷酸肌醇代谢是近端受体反应，实际上膜结合的磷脂酶C可能对其他肾上腺素能受体发挥类似于腺苷酸环化酶的作用（Putney等人，1980）。然而，有一些证据表明在某些情况下α1受体可能直接刺激腺苷酸环化酶，并且已经报道了鸟嘌呤核苷酸对α1受体位点激动剂亲和力的调节作用。这些数据以及报道的Na+对α1受体的调节作用（Glossmann和Presek，1979；Glossmann等人，1981）的意义仍有待解决。（摘要截短至400字）
