AJP - Regulatory, Integrative and Comparative Physiology, Vol 251, Issue 3 531-R536, Copyright © 1986 by American Physiological Society
Control of renin secretion by Ca2+ and cyclic AMP through two parallel mechanisms
C. S. Park, D. H. Sigmon, D. S. Han, T. W. Honeyman and J. C. Fray
The cellular mechanism of action of cyclic AMP (cAMP) mediating the
beta-adrenergic stimulation of renin secretion was studied, with special
reference to its interactions with the inhibitory pathway of renin
secretion by Ca2+ calmodulin. Forskolin, a potent stimulator of adenyl
cyclase that bypasses the hormone-receptor interactions, stimulated renin
secretion in vitro from rabbit renal cortical slices in a
concentration-dependent manner. Renin secretion stimulated by submaximal
concentration of forskolin was partly or completely antagonized or blocked
by raising intracellular Ca2+ concentration by incubating slices in a
high-K+ depolarizing medium, but renin secretion stimulated by the maximal
effective concentration of forskolin was not inhibited by Ca2+. In
addition, the maximal effective concentration of forskolin (10(-5) M)
increased renin secretion by a fixed amount independent of medium (by
inference, intracellular) Ca2+ concentration in the range of 10(-8) to
10(-6) M in a high-K+ medium. Furthermore, the degree of stimulation of
renin secretion by forskolin was greater with greater removal of the
inhibitory effect of Ca2+ calmodulin pathway on renin secretion with use of
potent calmodulin antagonists, suggesting that the stimulatory effect of
cAMP on renin secretion may be maximal in the absence of the inhibitory
influence of Ca2+. These results are consistent with the hypothesis that
cAMP (by inference, the beta-adrenergic stimulus) stimulates renin
secretion through a cellular mechanism independent of that through the Ca2+
-calmodulin pathway.
