INTRACELLULAR CA2+ DEPLETION AND CA2+ CHANNEL BLOCKERS INCREASE RENALKALLIKREIN SECRETION

This study examined the effect of various manipulations of intracellul ar Ca2+ on kallikrein release by renal cortical slices. Increasing the extracellular Ca2+ concentration and the addition of Ca2+ ionophore A 23187 was without effect on kallikrein release. In contrast, kallikrei n release was enhanced by the addition of either extracellular or intr acellular Ca2+ chelators in Ca2+-free medium and by two Ca2+ channel b lockers, 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 C a2+ which was abolished by nifedipine whereas the stimulation of kalli krein secretion persisted, a direct stimulating effect of potassium, a t least at sub-physiological concentration, is suggested. Similarily, inhibition of either sodium/potassium-ATPase and Ca2+ ATPase by ouabai n and vanadium respectively, was also without effect on kallikrein sec retion. Taken together, these results indicate that intracellular Ca2 depletion, Ca2+ channel blockers and high extracellular K+ concentrat ions, acting through different mechanisms, are effective stimuli for k allikrein secretion, at least in the isolated renal cortical slice.