Dependence of Aldosterone Stimulation in Adrenal Glomerulosa Cells on Calcium Uptake: Effects of Lanthanum and Verapamil

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.