Atrial natriuretic peptide inhibition of calcium ionophore A23187-stimulated aldosterone secretion in rat adrenal glomerulosa cells.
The effect of atrial natriuretic peptide (ANP) on calcium ionophore A23187-stimulated aldosterone secretion was investigated using collagenase-dispersed rat adrenal glomerulosa cell suspensions. A23187 treatment induced a dose-dependent stimulation of aldosterone secretion, exhibiting an EC50 of approximately 75 nM. In agreement with the presumed action of A23187 as a Ca2+ ionophore, stimulation was dependent on the extracellular Ca2+ concentration, being completely inhibited in nominally Ca(2+)-free medium. In such Ca(2+)-free medium, stimulation of aldosterone secretion by bath applied 25-hydroxycholesterol was not inhibited, indicating that cells and biosynthetic pathway enzymes were not inhibited by low extracellular Ca2+ levels. A23187-induced aldosterone secretion was also inhibited by more than 90% when cells were simultaneously treated with ANP. Maximal ANP inhibition of A23187-stimulated aldosterone secretion was not overcome by concentrations of A23187 up to 10 microM or by increasing the extracellular Ca2+ concentration from 1.25 to 5 mM in the presence of A23187 and ANP. Addition of A23187 to ACTH-, angiotensin II-, or K(+)-stimulated glomerulosa cells did not overcome ANP-induced inhibition of aldosterone secretion stimulated by these secretagogues. In contrast to ANP inhibition of Ca(2+)-dependent A23187 stimulation of aldosterone secretion, ANP inhibition of dBcAMP-stimulated aldosterone secretion was readily overcome by increasing the dBcAMP concentration. These results indicated that ANP selectively and noncompetitively inhibited an intracellular step necessary for Ca(2+)-dependent stimulation of the early pathway of aldosterone biosynthesis in rat adrenal glomerulosa cells.
Lotshaw
D P
DP
Department of Medicine, Medical College of Ohio, Toledo 43699.
Franco-Saenz
R
R
Mulrow
P J
PJ
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism*
D006728:Hormones; D000451:Mineralocorticoid Receptor Antagonists; D000001:Calcimycin; D000450:Aldosterone; D003994:Bucladesine; D009320:Atrial Natriuretic Factor; D002118:Calcium