Using a continuous superfusion system of dog renal cortical slices, we studied the role of Ca2+ in the intracellular control mechanism for renin release. The calcium ionophore A23187 (10 muM) produced a significant decrease in renin release. This effect was abolished in the absence of extracellular Ca2+. Moreover, pretreatment with the calmodulin inhibitor W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, 20 muM) completely prevented the inhibitory effect of A23187 (10 muM). The beta-adrenoceptor agonist isoproterenol (1, 10 and 100 muM) produced a concentration-dependent increase in renin release. Pretreatment with W-7 (20 muM) potentiated the stimulation of renin release induced by isoproterenol (1 muM). These results suggest that A23187-induced inhibition of renin release is mediated by the activation of calmodulin via an increase in intracellular Ca2+ and beta-adrenoceptor-stimulated renin release is modulated by intracellular Ca2+ mobilization. (C) 2002 Elsevier Science B.V. All rights reserved.