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Am J Physiol Renal Physiol 251: F1055-F1062, 1986;
0363-6127/86 $5.00
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AJP - Renal Physiology, Vol 251, Issue 6 1055-F1062, Copyright © 1986 by American Physiological Society


ARTICLES

Involvement of calmodulin in mediating inhibitory action of intracellular Ca2+ on renin secretion

C. S. Park, T. W. Honeyman, E. S. Chung, J. S. Lee, D. H. Sigmon and J. C. Fray

This study sought to elucidate further the cellular mechanism(s) involved in the control of renin secretion by Ca2+. The rate of renin secretion in vitro by rabbit and dog renal cortical slices was inversely related to medium Ca2+ concentration. The inverse relationship was observed only when the cell membrane permeability to Ca2+ was increased by K+ depolarization, suggesting that the Ca2+ concentration in the juxtaglomerular cell modulates renin secretion. From this relationship, renin secretion appears to turn on at intracellular Ca2+ concentrations between 10(-8) and 10(-7) M. Calmidazolium, a potent calmodulin antagonist, markedly stimulated basal renin secretion in a concentration-dependent manner. Pretreatment of slices with calmidazolium blocked the inhibition of renin secretion by high-K+ medium. Calmidazolium and several other calmodulin antagonists (W-7, W-13, and trifluoperazine) partly or fully reversed the inhibition of renin secretion previously inhibited by high-K+ medium in the order of their potencies as calmodulin antagonists. Indeed, W-5, a biologically inactive structural analogue of W-7, was without effect. These results support the hypothesis that renin secretion is inversely related to intracellular Ca2+ and that Ca2+ inhibits renin secretion by a calmodulin-dependent process.


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[Abstract] [Full Text] [PDF]




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