G. Bompart et al., INTRACELLULAR CA2+ DEPLETION AND CA2+ CHANNEL BLOCKERS INCREASE RENALKALLIKREIN SECRETION, European journal of pharmacology, 278(3), 1995, pp. 225-231
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.