Quantitative analysis of the cytosolic-free-Ca2+-dependency of aldosterone production in bovine adrenal glomerulosa cells. Different requirements for angiotensin II and K+. |
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| Authors: | A M Capponi P D Lew and M B Vallotton |
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| Affiliation: | Division of Endocrinology, University Hospital, Geneva, Switzerland. |
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| Abstract: | Angiotensin II (AII) and K+ raise the cytosolic free Ca2+ concentration ( Ca2+]i) and stimulate aldosterone production in isolated bovine adrenal glomerulosa cells. The mechanisms leading to an elevation of Ca2+]i were analysed with the fluorescent Ca2+ probe quin 2. (1) Whereas Ca2+]i rose transiently and returned to basal values within 5 min in response to AII, the effect of K+ was sustained for at least 15 min. (2) AII released Ca2+ from intracellular stores, whereas the Ca2+]i response to K+ depended solely on extracellular Ca2+]. (3) When added after K+ stimulation, AII provoked a dramatic decrease in Ca2+]i to below the resting value. The role of Ca2+]i in stimulating steroidogenesis was determined by manipulating the concentration of this cation. (4) In a cell superfusion system, the aldosterone response to AII is biphasic. Suppressing the transient Ca2+]i elevation triggered by AII resulted in the disappearance of the initial secretory peak, but the final production rate was similar to that of control cells. (5) Normal basal Ca2+]i levels were, however, necessary to maintain continuous AII-induced steroidogenesis. (6) When added after AII, the antagonist analogue Sar1,Ala8]AII suppressed steroidogenesis without affecting Ca2+]i levels. (7) In contrast, continuously elevated Ca2+]i values were required for the initiation and the maintenance of K+-stimulated aldosterone production. These results demonstrate important differences in the mechanisms through which AII and K+ activate the Ca2+ messenger system. Moreover, functional correlations have shown that K+, but not AII, depends solely on a sustained Ca2+]i response for its steroidogenic effect. However, the AII-induced effect is also a Ca2+-requiring process: the initial Ca2+]i transient accelerates the onset of steroidogenesis, which is subsequently extremely sensitive to Ca2+]i decreases below normal basal levels. |
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