Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells.
Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC50) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, we investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel "activator," without change in its EC50. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated 45Ca influx into isolated rat adrenal glomerulosa cells was studied. Basal calcium influx was not significantly affected by ANP or nifedipine. Angiotensin II-, ACTH-, potassium-, and BAY K8644-stimulated calcium influx were significantly decreased by 1 nM ANP or 30 microM nifedipine. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology
D000804:Angiotensin II; D000450:Aldosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D009543:Nifedipine; D011188:Potassium; D002118:Calcium