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Divergent pharmacological responses to 2 calmodulin inhibitors chlorpromazine and w 7 n 6 aminohexyl 5 chloro 1 naphthalenesulfonamide in pancreatic acinar cells

, : Divergent pharmacological responses to 2 calmodulin inhibitors chlorpromazine and w 7 n 6 aminohexyl 5 chloro 1 naphthalenesulfonamide in pancreatic acinar cells. Canadian Journal of Physiology & Pharmacology 62(3): 309-313

The possible role of calmodulin in exocytotic secretion is supported by the presence of this Ca-binding protein in secretory cells, and by the antisecretory effects in intact secretory cells of substances which can antagonize calmodulin-stimulated enzymes in broken cell preparations. In this study, 2 in vitro calmodulin antagonists, W-7 and chlorpromazine, produced both similar and different pharmacological effects on the secretory process in rat exocrine pancreas. Both substances blocked amylase secretion in response to carbachol or cholecystokinin octapeptide, but only chlorpromazine inhibited the ability of carbachol to stimulate 45Ca efflux from isotope-preloaded cells. Only W-7 could inhibit the secretory response to vasoactive intestinal peptide (VIP); both W-7 and chlorpromazine were equipotent partial antagonists of VIP-stimulated cAMP synthesis. Chlorpromazine increased the secretory response to melittin but W-7 did not. The divergence in biological responsiveness to W-7 and chlorpromazine makes it difficult to extrapolate the in vitro effects of these agents to similar actions in intact cell systems.


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