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.