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Department of Medicine, Medical College of Ohio Toledo, Ohio 43699
Address all correspondence and requests for reprints to: Dr. Patrick J. Mulrow, Department of Medicine, Medical College of Ohio, CS 10008, Toledo, Ohio 43699.
Abstract
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 Ca2+-free medium. In such Ca2+-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 µM 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 Ca2+-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 noncompetetively inhibited an intracellular step necessary for Ca2+-dependent stimulation of the early pathway of aldosterone biosynthesis in rat adrenal glomerulosa cells. (Endocrinology 129: 2305–2310, 1991)
Footnotes
* An abstract of these data was published previously in the Program of the 72nd Annual Meeting of The Endocrine Society, Atlanta, GA, 1990, p. 399. This work was supported in part by a grant from the American Heart Association, Ohio Affiliate, Inc. (Columbus, OH).
T. H. Morgan School of Biological Sciences, University of Kentucky, Lexington, Kentucky 40506–0225.
Received May 6, 1991.
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