Possible role of calmodulin in renin secretion from isolated rat kidneys and renal cells: studies with trifluoperazine.
Trifluoperazine, an inhibitor of calmodulin and calmodulin-directed secretion, was used to examine a possible role of calmodulin in renin secretion from isolated perfused kidneys and renal cortical cells. In isolated perfused kidneys trifluoperazine stimulated basal renin secretion in a dose-dependent manner, with 10 microM causing no stimulation and 50 microM causing 167% increase. Trifluoperazine potentiated the elevated renin secretion induced by isoprenaline and low Ca in isolated kidneys. In renal cortical cells trifluoperazine increased basal renin secretion and potentiated the secretion induced by Ca omission. Cells homogenized immediately after 1 h exposure to trifluoperazine had a substantial reduction in soluble renin without any effect on the change in granular renin. In the absence of trifluoperazine, soluble renin increased with O Ca and decreased with 1.5 mM-Ca. It is concluded that trifluoperazine stimulates renin secretion by a cellular mechanism possibly at the level of the juxtaglomerular cell. It is suggested that the role of trifluoperazine, and by inference calmodulin, in the secretion of renin may be quite different from its role in secretion of several other substances.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000166:cytology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology*
D002147:Calmodulin; D014268:Trifluoperazine; D012083:Renin; D007545:Isoproterenol; D002118:Calcium