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.
Bompart
G
G
Institut National de la Santé et de la Recherche Médicale, U388, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
Tack
I
I
Bascands
J L
JL
Girolami
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007610:Kallikreins / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism*; D007705:Kinins / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D007705:Kinins; D007610:Kallikreins; D002118:Calcium