Hypothyroidism modulates beta adrenergic receptor adenylate cyclase interactions in rat reticulocytes.
Hypothyroidism modulates beta adrenergic receptor adenylate cyclase interactions in rat reticulocytes.
复制标题
甲状腺功能减退症调节大鼠网织红细胞中β肾上腺素能受体腺苷酸环化酶的相互作用。
DOI：
10.1172/jci110397
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Lefkowitz,RJ
中科院分区：
文献类型：
--
作者：
Stiles,GL;Stadel,JM;DeLean,A;Lefkowitz,RJ
我们研究了因甲状腺切除术导致甲状腺功能减退的动物中大鼠网织红细胞β肾上腺素能受体结合位点的变化。通过测量(-)[3H]-二氢阿普洛尔结合位点的数量和激动剂竞争占据受体的能力来评估β肾上腺素能受体相互作用。甲状腺功能减退动物的细胞中受体的数量显着减少。此外，结合存在显着的激动剂特异性改变。使用计算机辅助曲线拟合技术，发现(-)异丙肾上腺素稳定高亲和力鸟嘌呤核苷酸敏感的“偶联”形式受体的能力受到损害。此外，根据霍乱毒素催化 ADP 核糖基化的 42,000 个 Mr 底物的数量评估，来自甲状腺功能减退动物的网织红细胞的核苷酸调节蛋白浓度降低。这些改变与儿茶酚胺和 NaF 刺激的腺苷酸环化酶活性的降低有关。 β 肾上腺素能受体与腺苷酸环化酶系统其他调节成分的耦合减弱代表了甲状腺状态改变调节 β 肾上腺素能受体功能和组织的 β 肾上腺素能反应性的机制。
We have investigated alterations in beta adrenergic receptor binding sites of rat reticulocytes occurring in animals rendered hypothyroid by thyroidectomy. Beta adrenergic receptor interactions were assessed by measuring the number of (-)[3H]-dihydroalprenolol binding sites and the ability of an agonist to compete for occupancy of the receptors. The number of receptors was significantly reduced in cells from the hypothyroid animals. In addition, there were significant agonist-specific alterations in binding. Using computer assisted curve fitting techniques, it was found that the ability of (-)isoproterenol to stabilize a high affinity guanine nucleotide sensitive "coupled" form of the receptor was impaired. Reticulocytes from hypothyroid animals have, in addition, a reduction in the concentration of the nucleotide regulatory protein as assessed by the number of 42,000 Mr substrates for cholera toxin catalyzed ADP ribosylation. These alterations are associated with reductions in catecholamine and NaF stimulated adenylate cyclase activity. Diminished coupling of beta adrenergic receptors with other regulatory components of the adenylate cyclase system represents a mechanism by which altered thyroid states modulate beta adrenergic receptor function and beta adrenergic responsiveness of tissues.Images