Intracellular Ca2+ contributes to K+-induced increase in renal kallikrein secretion

We have reported that natriuretic effects of K+ are involved in enhancement of renal kallikrein–kinin system. The study was aimed to examine 1) comparison of augmentative effects of K+ on urinary KK excretion with non-specific washout effects by trichlormethiazide (thiazide), polyethyleneglycol 200 (PEG) and rapid physiological saline infusion, 2) contribution of Ca2+ on the K+-induced increase in renal kallikrein secretion. Renal kallikrein activities were measured as fluorescence activities of methylcoumarinylamide-labeled synthetic substrate of tissue kallikrein (TK). Increases in urinary TK excretion were simultaneously observed with diuresis caused by thiazide, PEG, and rapid saline infusion. K+ infusion increased urinary TK excretion with a diuretic response same as the control. K+, but not thiazide, showed an early increase in renal TK secretion dose dependently in the kidney slices. Increases in renal TK secretion persisted during treatment with K+. Neither voltage-dependent Ca2+-channel blockers such as verapamil and nifedipine nor simultaneous treatment of EDTA affected on the K+-induced increase in renal TK secretion. While, EDTA decreased the K+-induced increases in renal TK secretion with time. Caffeine also had an early effect on the increase in renal TK secretion. K+-induced increases in renal TK secretion was demonstrated even after treatment with ryanodine or depletion of caffeine-sensitive intracellular Ca2+ by thapsigargin. It was indicated that the increase in renal TK secretion by K+ depends on the intracellular Ca2+ and the caffeine-sensitive release of intracellular Ca2+ may not be involved in this response. Mechanisms for the K+-induced increase in renal TK secretion needs to be further elucidated.