HETEROGENEITY OF ALPHA-2 ADRENERGIC RECEPTORS

α-2肾上腺素能受体介导的几个重要功能， 中枢和外周神经系统的内源性儿茶酚胺 系统. 几种临床上重要的药物似乎产生它们的 通过与α-2受体的相互作用产生药理作用。 那里 现在有相当多的证据表明， 哺乳动物α-2的药理学特性和调节 肾上腺素能受体来自各种组织和物种。 我们建议 药理学特性和调节的差异 （作用机制）的α-2肾上腺素能受体可能是由于 α-2肾上腺素能受体复合物结构的差异。 为了检验这一假设，建议在各种组织中进行比较， 物种：（1）各种肾上腺素能药物的等级顺序和相对效价 药物使用放射性配体结合和功能测定;（2）热 放射性配体结合的稳定性和最适pH;（3）放射性配体的功能大小 受体复合物使用靶分析（辐射灭活）;（4） 凝胶过滤法测定表观分子大小 密度梯度离心溶解在 激动剂的存在和不存在;和（5）表观分子量 部分纯化受体的SDS凝胶电泳 光亲和探针 这些研究应该有助于解决目前的问题。 α受体分类混乱，可能导致更多 临床应用的选择性α肾上腺素能药物。

Alpha-2 adrenergic receptors mediate several important functions of the endogenous catecholamines in both the central and peripheral nervous systems. Several clinically important drugs appear to produce their pharmacologic effects through an interaction at alpha-2 receptors. There now exists considerable evidence indicating significant differences in the pharmacological characteristics and regulation of mammalian alpha-2 adrenergic receptors from various tissues and species. We suggest that differences in the pharmacological properties and in the regulation (mechanism of action) of alpha-2 adrenergic receptors may be due to differences in the structure of the alpha-2 adrenergic receptor complex. To test this hypothesis, it is proposed to compare in various tissues and species: (1) The rank order and relative potencies of various adrenergic drugs using both radioligand binding and functional assays; (2) The thermal stability and pH optima of radioligand binding; (3) The functional size of the receptor complex using target analysis (radiation inactivation); (4) The apparent molecular size determined by gel filtration and sucrose density gradient centrifugation of receptor preparations solubilized in the presence and absence of agonist; and (5) The apparent molecular weight from SDS gel electrophoresis of partially purified receptors labeled with a photoaffinity probe. These studies should help to resolve the present confusion in classification of alpha receptors and may lead to more selective alpha adrenergic drugs for clinical use.