A comparison was made of the effects of angiotensin II (ANG II) and K+ on aldosterone secretion and calcium efflux from porcine adrenal glomerulosa cells. In the presence of 1.25 mM Ca2+ in the perifusion medium, both 1 x 10(-9) M ANG II and 12 mM K+ caused a 3-fold increase in rate of aldosterone secretion. ANG II caused a 3.5-fold increase in the fractional efflux ratios of radiocalcium from cells prelabeled with 45Ca, but K+ caused only a 1.5-fold increase. When the perifusate contained no Ca2+ or the Ca2+ was replaced by 0.6 mM Sr2+, the effects of K+ on both 45Ca efflux and aldosterone production were abolished. On the other hand, ANG II still caused approximately the same increase in the fractional efflux ratio of radiocalcium and 25-50% of the normal increase in aldosterone production rate. When the perifusate contained 1.25 mM calcium and 25 microM dantrolene, K+ produced the same 1.5-fold increase in calcium efflux and the same maximal rate of aldosterone production as seen in the absence of dantrolene. In contrast, dantrolene greatly inhibited ANG II-induced increase in the fractional efflux ratio of calcium, 1.5-fold compared with 3.5-fold in the absence of dantrolene. Likewise, dantrolene delayed the onset of the ANG II-induced increase in aldosterone secretion and reduced the maximal rate of secretion to 50%. Cells incubated with both dantrolene and media containing no Ca2+ or containing Sr2+ in place of Ca2+ showed no response to ANG II either in terms of calcium efflux or aldosterone production.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of cAMP accumulation on ATP-dependent priming and Ca(2+)-dependent fusion in Ca(2+)-regulated exocytosis were examined in antral mucous cells of guinea pigs by using video-enhanced contrast microscopy. The Ca(2+)-regulated exocytosis activated by 1 microM ACh consisted of two phases, an initial transient phase followed by a sustained phase, which were potentiated by cAMP accumulation. Depletion of ATP by 100 microM dinitrophenol (uncoupler of oxidative phosphorylation) or anoxia induced the sustained phase without the initial transient phase in Ca(2+)-regulated exocytosis. However, accumulation of cAMP before depletion of ATP induced and potentiated an initial transient phase followed by a sustained phase in Ca(2+)-regulated exocytosis. This suggests that the initial transient phase of Ca(2+)-regulated exocytosis is induced by fusion of all primed granules maintained by ATP and that accumulation of cAMP accelerates ATP-dependent priming of the exocytotic cycle. Moreover, ACh and Ca(2+) dose-response studies showed that accumulation of cAMP shifted the dose-response curves to the low concentration side, suggesting that it increases Ca(2+) sensitivity in the fusion of the exocytotic cycle. In conclusion, cAMP accumulation increases the number of primed granules and Ca(2+) sensitivity of the fusion, which potentiates Ca(2+)-regulated exocytosis in antral mucous cells.
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