Intracellular Ca2+ depletion and Ca2+ channel blockers increase renal kallikrein secretion

This study examined the effect of various manipulations of intracellular Ca2+ on kallikrein release by renal cortical slices. Increasing the extracellular Ca2+ concentration and the addition of Ca2+ ionophore A23187 was without effect on kallikrein release. In contrast, kallikrein release was enhanced by the addition of either extracellular or intracellular Ca2+ chelators in Ca(2+)-free medium and by two Ca2+ channel blockers, verapamil and nifedipine. Kallikrein release was also highly enhanced in depolarising medium (10-100 mM potassium chloride). Since potassium chloride induced a dose-related increase in free cytosolic Ca2+ which was abolished by nifedipine whereas the stimulation of kallikrein secretion persisted, a direct stimulating effect of potassium, at least at sub-physiological concentration, is suggested. Similarily, inhibition of either sodium/potassium-ATPase and Ca2+ ATPase by ouabain and vanadium respectively, was also without effect on kallikrein secretion. Taken together, these results indicate that intracellular Ca2+ depletion, Ca2+ channel blockers and high extracellular K+ concentrations, acting through different mechanisms, are effective stimuli for kallikrein secretion, at least in the isolated renal cortical slice.