Regulation of the PTH-receptor-cyclase system of canine kidney: effects of calcium, magnesium, and guanine nucleotides.
Regulation of the PTH-receptor-cyclase system of canine kidney: effects of calcium, magnesium, and guanine nucleotides.
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犬肾 PTH 受体环化酶系统的调节：钙、镁和鸟嘌呤核苷酸的影响。
DOI：
10.1152/ajprenal.1981.241.4.f364
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Martin,KJ
中科院分区：
文献类型：
--
作者：
Bellorin-Font,E;Martin,KJ
这些研究考察了钙、镁和鸟嘌呤核苷酸与甲状旁腺素与肾受体的结合和腺苷环化酶在纯化制备的肾皮质基底膜中的相互作用。在甲状旁腺素存在的情况下，增加钙离子浓度对腺苷酸环化酶活性的抑制比基础活性的抑制更明显。这种作用不能用钙离子对甲状旁腺素平衡结合或结合亲和力的影响来解释。甲状旁腺素的存在也降低了酶对镁离子的需求，与钙离子和镁离子相互作用的竞争性相一致。鸟嘌呤核苷酸对酶活性的金属需求也产生了类似的变化。然而，尽管甲状旁腺素和鸟嘌呤核苷酸在总酶活性上有显著的协同作用，但在这方面并不是相加的。为了进一步确定鸟嘌呤核苷酸对受体-环化酶系统的影响，还进行了其他研究。GTP和GPP(NH)p使甲状旁腺素的平衡结合呈剂量依赖性下降，半最大位移略有增加。甲状旁腺激素刺激的腺苷环化酶活性被任一核苷酸显著增强，且半最大活性降低(GPP(NH)p大于GTP)。这部分是由于鸟嘌呤核苷酸对受体结合的甲状旁腺素解离率的显著影响。这些数据表明，Ca~(2+)对PTH刺激的腺苷环化酶活性的抑制不是由于PTH结合的减少，而是PTH对核苷酸调节部位腺苷环化酶激活的金属需求的影响。
These studies examine the interactions of Ca2+, Mg2+, and guanine nucleotides with PTH binding to renal receptors and activation of adenylate cyclase in a purified preparation of basolateral renal cortical membranes. Inhibition of adenylate cyclase activity by increasing concentrations of CA2+ was more pronounced in the presence of PTH than on basal activity. This effect was not explained by an effect of Ca2+ on equilibrium PTH binding or binding affinity. The presence of PTH also decreased the requirements of the enzyme for Mg2+, consistent with the competitive nature of Ca2+ and Mg2+ interaction. Guanine nucleotides produced similar changes in the metal requirements for enzyme activity. PTH and guanine nucleotides, however, were not additive in this regard in spite of marked synergism in total enzyme activity. Additional studies were performed to further define the effects of guanine nucleotides on the receptor-cyclase system. GTP and Gpp(NH)p caused a dose-dependent decline in equilibrium PTH binding and a small increase in half-maximal displacement. PTH-stimulated adenylate cyclase activity was markedly increased by either nucleotide, and the half-maximal activity was decreased (Gpp(NH)p greater than GTP). This was partly explained by a marked effect of guanine nucleotides on the dissociation rate of receptor-bound PTH. These data suggest that Ca2+ inhibition of PTH-stimulated adenylate cyclase activity is not due to a decreased binding of PTH but to an effect of PTH on the metal requirements for adenylate cyclase activation at the nucleotide regulatory site.