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

Abstract

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.