Calmodulin antagonists stimulate renin release from isolated rat glomeruli.
Effects of calmodulin antagonists on renin release from isolated rat glomeruli were examined. The calmodulin antagonists used were N-(6-aminohexyl)-5-chloro-naphthalene-1-sulfonamide (W-7), triflupromazine and trifluoperazine. These drugs induced renin release from isolated glomeruli in a dose-dependent manner. The threshold concentration for renin release in the calcium-containing medium was 50 microM for W-7, 5 microM for triflupromazine and 2 microM for trifluoperazine respectively. The threshold concentrations were 2-5 times less in the calcium-free medium. The maximum levels of renin release by the three antagonists were similar in both calcium-containing and calcium-free media. In the absence of these antagonists, the basal rate of renin release in the calcium-free medium was markedly higher than in the calcium-containing medium. These results suggest that the calcium-calmodulin system inhibits renin release and that renin release is regulated by a mechanism different from the calcium-stimulated exocytotic mechanism by which many hormones are released.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D007545:Isoproterenol / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*; D014273:Triflupromazine / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D013449:Sulfonamides; D014268:Trifluoperazine; C017967:W 7; D012083:Renin; D007545:Isoproterenol; D014273:Triflupromazine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine