Inhibitory effects of calmodulin antagonists on isoproterenol- and dibutyryl cyclic AMP-stimulated amylase release from rat parotid acinar cells.

Abstract

The effects of three calmodulin antagonists on rat parotid amylase release were investigated in vitro using a dispersed acinar cell preparation. The potent calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), inhibited both 1 microM isoproterenol (ISO)- and 1 mM dibutyryl cyclic AMP (DBcAMP)-stimulated amylase release in a dose-dependent manner at concentrations of 25-100 microM. The IC50 values for the ISO-stimulated amylase release were 22 microM with TFP and 42 microM with W-7, and the values for the DBcAMP-stimulated release were 25 microM and 48 microM, respectively. The weak calmodulin antagonist, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), caused only slight inhibition at a concentration of 100 microM. These calmodulin antagonists only had a very small effect on the spontaneous release of lactate dehydrogenase. The results suggest that the calcium-calmodulin system may play a role in the exocytotic process of amylase release from the rat parotid gland.