Bär H P, Hechter O
Proc Natl Acad Sci U S A. 1969 Jun;63(2):350-6. doi: 10.1073/pnas.63.2.350.
A large number of hormones, of diverse molecular structure, evoke characteristic responses in target cells via the intermediary 3',5'-AMP, the specificity of hormone action upon cell type being achieved by selective stimulation of adenyl cyclase. In the fat cells of rat adipose tissue, adenyl cyclase is stimulated by a number of hormones of disparate molecular structure, posing the question whether this cell type posesses multiple cyclase systems with distinctive specificities for individual hormones, or a single cyclase with broad specificity to a variety of hormones. Studies of the stimulatory effects of adenocorticotropin, glucagon, and epinephrine upon the adenyl cyclase of the rat fat cell "ghosts" (plasma membrane sacs) have shown that distinctive selectivity sites for each of these hormones can be differentiated. The beta-adrenergic blocking agent Kö 592 abolished the stimulatory effect of epinephrine without influencing adenocorticotropin or glucagon; Ca was required for adenocorticotropin action, but not for glucagon or epinephrine. Dose-response curves show that the affinity of hormones to the cyclase system was in the order: glucagon > adenocorticotropin >> epinephrine; the magnitude of cyclase activation by maximal doses of hormones had a reversed order. Combinations of maximal doses of hormones failed to produce additive stimulation. The results show that in the membrane of the fat cell a single catalytic unit of adenyl cyclase is coupled to distinctive selectivity sites for three lipolytic hormones.
大量分子结构各异的激素通过中间物质3',5'-AMP在靶细胞中引发特征性反应，激素对细胞类型作用的特异性是通过对腺苷酸环化酶的选择性刺激来实现的。在大鼠脂肪组织的脂肪细胞中，腺苷酸环化酶受到多种分子结构不同的激素刺激，这就提出了一个问题：这种细胞类型是拥有对个别激素具有独特特异性的多个环化酶系统，还是具有对多种激素具有广泛特异性的单一环化酶。对促肾上腺皮质激素、胰高血糖素和肾上腺素对大鼠脂肪细胞“幽灵”（质膜囊泡）的腺苷酸环化酶的刺激作用的研究表明，这些激素各自独特的选择性位点是可以区分的。β-肾上腺素能阻断剂Kö 592消除了肾上腺素的刺激作用，而不影响促肾上腺皮质激素或胰高血糖素；促肾上腺皮质激素的作用需要钙，但胰高血糖素或肾上腺素的作用不需要钙。剂量-反应曲线表明，激素对环化酶系统的亲和力顺序为：胰高血糖素>促肾上腺皮质激素>>肾上腺素；最大剂量激素激活环化酶的程度顺序则相反。最大剂量激素的组合未能产生相加刺激作用。结果表明，在脂肪细胞膜中，腺苷酸环化酶的单个催化单位与三种脂解激素的独特选择性位点相偶联。
