HETEROGENEITY OF ALPHA-2 ADRENERGIC RECEPTORS

α-2肾上腺素能受体介导的几个重要功能 中枢神经和外周神经内源性儿茶酚胺 系统。几种临床上重要的药物似乎产生了 通过α-2受体的相互作用产生的药理效应。那里 现在有相当多的证据表明，在 哺乳动物α-2的药理特性及其调控 来自各种组织和物种的肾上腺素能受体。我们建议 药理性质及调控上的差异 α2肾上腺素能受体的(作用机制)可能是由于 α-2肾上腺素能受体复合体结构的差异。 为了验证这一假设，建议在不同的组织和 物种：(1)各种肾上腺素能激素的等级顺序和相对效力 使用放射性配基结合和功能分析的药物；(2)热分析 放射性配基结合的稳定性和最适pH；(3)功能大小 受体复合体靶向分析(辐射灭活)；(4) 凝胶过滤和蔗糖测定的表观分子尺寸 密度梯度离心法测定增溶的受体制剂 存在和不存在激动剂；以及(5)来自 部分纯化的A标记受体的十二烷基硫酸钠凝胶电泳法 光亲和探针。这些研究应该有助于解决目前的问题 对阿尔法受体分类的混淆，可能导致更多 临床使用的选择性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.