Fakunding J L, Catt K J
Endocrinology. 1980 Nov;107(5):1345-53. doi: 10.1210/endo-107-5-1345.
The calcium dependence of steroidogenic responses to angiotensin II, potassium, and ACTH was analyzed in isolated adrenal glomerulosa cells incubated with inhibitors of calcium uptake. Both lanthanum and verapamil reduced the stimulation of aldosterone production by each regulator in a dose-dependent manner, with only a moderate decrease in basal steroid production. The stimulation of aldosterone and cAMP production by ACTH was blocked by both antagonists, and the degree of inhibition was dependent on the concentration of ACTH employed. Increasing concentrations of verapamil caused an increase in th ACTH concentration required for half-maximal stimulation as well as a reduction in the maximum production of aldosterone. Aldosterone production by glomerulosa cells in response to angiotensin II or potassium was also decreased by lanthanum and verapamil, with no change in the concentration of angiotensin II required for half-maximal stimulation of steroidogenesis. Stimulation of pregnenolone synthesis by angiotensin II was also inhibited by verapamil, indicating that calcium is required for the action of angiotensin II at an early step in the steroidogenic pathway. The inhibitory action of verapamil upon angiotensin-stimulated aldosterone production was overcome by increasing concentrations of calcium. Neither of the calcium antagonists affected the binding of angiotensin II to glomerulosa cells, placing the calcium requirement for the action of angiotensin II at a postreceptor locus. These results provide further evidence that angiotensin II and potassium increase aldosterone production in adrenal glomerulosa cells through a calcium-dependent mechanism, and indicate that calcium uptake is an essential requirement for the stimulation of aldosterone production by these two effectors.
在与钙摄取抑制剂一起孵育的分离肾上腺球状带细胞中，分析了对血管紧张素II、钾和促肾上腺皮质激素的类固醇生成反应的钙依赖性。镧和维拉帕米均以剂量依赖性方式降低了每种调节剂对醛固酮生成的刺激作用，而基础类固醇生成仅适度降低。两种拮抗剂均阻断了促肾上腺皮质激素对醛固酮和环磷酸腺苷生成的刺激作用，抑制程度取决于所用促肾上腺皮质激素的浓度。维拉帕米浓度增加导致半最大刺激所需的促肾上腺皮质激素浓度增加，同时醛固酮的最大生成量减少。镧和维拉帕米也降低了球状带细胞对血管紧张素II或钾的反应所产生的醛固酮，而类固醇生成半最大刺激所需的血管紧张素II浓度没有变化。维拉帕米也抑制了血管紧张素II对孕烯醇酮合成的刺激作用，表明在类固醇生成途径的早期步骤中，血管紧张素II的作用需要钙。增加钙浓度可克服维拉帕米对血管紧张素刺激的醛固酮生成的抑制作用。两种钙拮抗剂均不影响血管紧张素II与球状带细胞的结合，表明血管紧张素II作用的钙需求位于受体后位点。这些结果进一步证明，血管紧张素II和钾通过钙依赖性机制增加肾上腺球状带细胞中的醛固酮生成，并表明钙摄取是这两种效应物刺激醛固酮生成的必要条件。
