Intracellular Ca 2+ contributes to K +-induced increase in renal kallikrein secretion

Abstract

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 Ca 2+ 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 Ca 2+-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 Ca 2+ by thapsigargin. It was indicated that the increase in renal TK secretion by K + depends on the intracellular Ca 2+ and the caffeine-sensitive release of intracellular Ca 2+ may not be involved in this response. Mechanisms for the K +-induced increase in renal TK secretion needs to be further elucidated.