Calcium-dependent regulation of aldosterone production in isolated adrenal glomerulosa cells: effects of the ionophore A-23187.
The effect of the calcium ionophore A-23187 on the regulation of aldosterone synthesis was investigated in isolated rat adrenal glomerulosa cells. Over the concentration range of 0.1--1.0 microM, A-23187 increased aldosterone production in a dose-dependent manner, with half-maximal stimulation at approximately 0.3 microM. Stimulation of aldosterone production by A-23187 was dependent on the concentration of extracellular calcium and was not accompanied by detectable increases in cAMP production. In contrast to the stimulation of steroidogenesis elicited by A-23187 alone, the ionophore significantly inhibited the aldosterone responses to angiotensin II and potassium. In angiotensin II-stimulated cells, 0.2 microM A-23187 caused half-maximal inhibition of aldosterone production, and 2 microM A-23187 inhibited aldosterone production by about 70%. The ionophore did not affect the binding of angiotensin II to isolated glomerulosa cells and did not change the sensitivity of the cells to either angiotensin II or potassium. However, A-23187 reduced the total amount of steroid produced in response to these stimuli, most markedly when the extracellular calcium concentration was less than 0.4 mM. These results indicate that although A-23187 partially inhibits the steroidogenic responses to angiotensin II and potassium, the increases in cytosolic calcium caused by submicromolar ionophore concentrations result in stimulation of aldosterone production by adrenal zona glomerulosa cells.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D000900:Anti-Bacterial Agents; D000804:Angiotensin II; D000001:Calcimycin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium