Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites.
Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites.
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儿茶酚胺诱导的腺苷酸环化酶不敏感与β-肾上腺素能受体结合位点的丧失相关。
DOI：
10.1073/pnas.72.5.1945
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发表时间：
1975
影响因子：
11.1
通讯作者：
R. Lefkowitz
中科院分区：
文献类型：
--
作者：
C. Mukherjee;M. Caron;R. Lefkowitz
给青蛙注射β-肾上腺素能儿茶酚胺1-24小时，可使红细胞膜腺苷酸环化酶[ATP焦磷酸裂解酶（环化）; EC 4.6.1.1.]异丙肾上腺素体外刺激。次致敏是特定的儿茶酚胺刺激，因为基础和氟化物刺激的酶活性不受影响。异丙肾上腺素刺激的腺苷酸环化酶最大活性在异丙肾上腺素治疗的动物中下降了75%（P小于0.001）。然而，引起腺苷酸环化酶一半最大激活的异丙肾上腺素浓度不变。（-）[~ 3 H]Alprenolol是一种有效的竞争性β-肾上腺素能拮抗剂，用于直接研究对照和亚致敏动物红细胞膜上的β-肾上腺素能受体结合位点。在给药动物中，发现β-肾上腺素能受体结合位点（“特异性”（-）[3 H]阿普洛尔结合位点）的数量显著（P <0.005）下降60%。这些数据表明，β-肾上腺素能儿茶酚胺能够调节体内组织的儿茶酚胺敏感性，通过调节β-肾上腺素能受体结合位点的性质。
Injection of frogs with beta-adrenergic catecholamines for 1-24 hr produces marked subsensitivity of the erythrocyte membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1.] to in vitro stimulation by isoproterenol. The subsensitization is specific for catecholamine stimulation, since basal and fluoride-stimulated enzyme activity are unaffected. Maximum isoproterenol-stimulated adenylate cyclase activity declines by 75% in the isoproterenol-treated animals (P less than 0.001). The concentration of isoproterenol causing one-half maximal activation of adenylate cyclase, however, is unaltered. (-)[3H]Alprenolol, a potent competitive beta-adrenergic antagonist, was used to study directly the beta-adrenergic receptor binding sites in the erythrocyte membranes from control and subsensitized animals. A highly significant (P less than 0.005) 60% fall in the number of the beta-adrenergic receptor binding sites ("specific"(-)[3H]alprenolol binding sites) in the treated animals was found. The binding affinity of the sites was not markedly altered. These data suggest that beta-adrenergic catecholamines are able to regulate catecholamine sensitivity of tissues in vivo, by regulating the properties of the beta-adrenergic receptor binding sites.