Differential effects of cholera toxin on guanine nucleotide regulation of beta-adrenergic agonist high affinity binding and adenylate cyclase activation in frog erythrocyte membranes.

J M Stadel, R J Lefkowitz
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Abstract

The guanine nucleotide regulatory protein(s) regulates both adenylate cyclase activity and the affinity of adenylate cyclase-coupled receptors for hormones or agonist drugs. Cholera toxin catalyzes the covalent modification of the nucleotide regulatory protein of adenylate cyclase systems. Incubation of frog erythrocyte membranes with cholera toxin and NAD+ did not substantially alter the dose dependency for guanine nucleotide activation of adenylate cyclase activity. In contrast, toxin treated membranes demonstrated a 10 fold increase in the concentrations of guanine nucleotide required for a half maximal effect in regulating beta-adrenergic receptor affinity for the agonist (+/-) [3H]hydroxybenzylisoproterenol. The data emphasize the bifunctional nature of the guanine nucleotide regulatory protein and suggest that distinct structural domains of the guanine nucleotide regulatory protein may mediate the distinct regulatory effects on adenylate cyclase and receptor affinity for agonists.

霍乱毒素对鸟嘌呤核苷酸调节β -肾上腺素能激动剂高亲和力结合和腺苷酸环化酶在青蛙红细胞膜上活化的差异影响。
鸟嘌呤核苷酸调节蛋白(s)调节腺苷酸环化酶活性和腺苷酸环化酶偶联受体对激素或激动剂药物的亲和力。霍乱毒素催化腺苷酸环化酶系统的核苷酸调节蛋白的共价修饰。用霍乱毒素和NAD+孵育青蛙红细胞膜并没有实质性地改变鸟嘌呤核苷酸激活腺苷酸环化酶活性的剂量依赖性。相比之下,毒素处理的膜显示,鸟嘌呤核苷酸浓度增加10倍,才能达到调节β -肾上腺素能受体对激动剂(+/-)[3H]羟基苯基异丙肾上腺素亲和力的一半最大效果。这些数据强调了鸟嘌呤核苷酸调节蛋白的双功能性质,并表明鸟嘌呤核苷酸调节蛋白的不同结构域可能介导对腺苷酸环化酶和受体对激动剂亲和力的不同调节作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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