PIRENZEPINE: A RELATIVELY WEAK ANTAGONIST OF MUSCARINIC RECEPTOR IN ISOLATED MOUSE PANCREATIC ACINI

Abstract

The effects of pirenzepine, a selective antimuscarinic agent, on both carbachol-stimulated amylase release and [3H]N-methyl scopolamine ([3H]NMS) binding were studied in isolated mouse pancreatic acini. Pirenzepine at concentrations between 0.1-3.0 μM was found to inhibit carbachol-stimulated amylase release without any appreciable effect on the basal amylase secretion. The inhibition by pirenzepine was rapid and reversible. Biphasic dose-response curves to carbachol for amylase release shifted to the right with an increase in pirenzepine concentration, and pA2 value was estimated to be 6.8. IC50 of pirenzepine for carbachol-stimulated amylase release was 440 nM, and the potency of pirenzepine on the inhibition of amylase release was 2% relative to atropine. The effect of pirenzepine was selective for carbachol; amylase release stimulated by other secretagogues such as cholecystokinin (CCK), bombesin and Ca2+ ionophore A23187, was not affected by pirenzepine. In addition, pirenzepine was found to inhibit the specific binding of [3H]NMS, a muscarinic antagonist, to mouse pancreatic acini. The potency of pirenzepine in this action was 1% relative to atropine. The inhibitory effect of pirenzepine on receptor binding was selective for the muscarinic receptor. These results indicate that pirenzepine is a specific but relatively weak antagonist of muscarinic receptor in mouse pancreatic acini.