Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.
Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.
复制标题
肾腺苷酸环化酶以及甲状旁腺激素和维生素 D 在调节尿磷酸盐和腺苷环状 3,5-单磷酸排泄中的相互关系。
DOI：
--
复制
发表时间：
1976
影响因子：
15.9
通讯作者：
C. S. Anast
中科院分区：
文献类型：
--
作者：
L. R. Forte;G. Nickols;C. S. Anast
本研究探讨了维生素D缺乏大鼠的甲状旁腺激素磷酸尿反应中的环磷酸腺苷的作用。输注纯化的牛甲状旁腺激素（13.3 μ g/h）到控制，D-喂养，或D-缺乏，甲状腺甲状旁腺切除大鼠产生的肾磷酸盐和环AMP排泄增加6倍D-喂养大鼠，但只有两个参数增加2 - 3倍D-缺乏动物。静脉注射甲状旁腺激素的剂量范围从1-50 μ g/kg导致磷酸盐和环AMP排泄与D-喂养和D-缺乏甲状腺甲状旁腺切除大鼠剂量依赖性增加。然而，D-缺乏大鼠对这些甲状旁腺激素的注射有反应，在最高剂量50 μ g/kg时，肾磷酸盐和环AMP排泄增加2 - 3倍，而D-喂养动物的反应分别是磷酸盐和环AMP对照排泄水平的35倍和11倍。为了直接研究肾皮质腺苷酸环化酶系统的作用，在钝化磷酸尿和尿环磷酸腺苷的反应，甲状旁腺激素在D-缺乏大鼠，我们准备了一个质膜馏分富含这种酶活性的D-喂养和D-缺乏甲状腺甲状旁腺切除大鼠的肾皮质。肾皮质腺苷酸环化酶的D-缺乏大鼠显示显着（P <0.001）激活甲状旁腺激素的激素浓度范围从0.3至7.0 μ g/ml比观察到的D-饲养动物制备的酶。基础腺苷酸环化酶活性和氟化物刺激的酶活性没有改变的D-缺乏的状态。这些实验表明，在D缺乏大鼠中观察到的对甲状旁腺激素的磷酸尿反应减弱与肾皮质腺苷酸环化酶对该激素的反应性降低有关。此外，肾膜腺苷酸环化酶系统中的缺陷似乎定位于PTH与膜受体结合的水平，或者替代地，定位于PTH-受体结合信号传递至该膜酶的催化部分的水平。
This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 mug/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two- to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 mug/kg resulted in a dose-dependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two- to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 mug/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P less than 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 mug/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme.