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 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.
Fujita
Tomoe
T
Department of Pharmacology, Kitasato University, School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan. tomoe@kitasato-u.ac.jp
Ogino
Michiko
M
Daigo
Futaba
F
Yamaguchi
Tomoko
T
Majima
Masataka
M
D000818:Animals; D002118:Calcium / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology*; D007610:Kallikreins / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049971:Thiazides / Q000494:pharmacology
D049971:Thiazides; D011092:Polyethylene Glycols; D007610:Kallikreins; D011188:Potassium; D002118:Calcium