Effect of a new cholinergic agonist, aclatonium napadisilate, on exocrine and endocrine rat pancreas

Abstract

The effect of aclatonium napadisilate, a choline sulfonate derivative, on exocrine and endocrine pancreatic functions was compared with that of carbamylcholine in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, aclatonium napadisilate and carbamylcholine stimulated amylase release. While the relative efficacy of aclatonium napadisilate was the same as that of carbamylcholine, aclatonium napadisilate was about 20-fold less potent. In the isolated perfused pancreas, 0.1 microM or higher concentrations of aclatonium napadisilate elicited a significant insulin release in the presence of 8.3 mM glucose, whereas an appreciable increase in pancreatic exocrine secretion was obtained with a 10 times higher concentration (1.0 microM). In contrast, carbamylcholine did not stimulate insulin release at a dose (0.1 microM) that stimulated pancreatic exocrine secretion. The insulin-releasing effect of aclatonium napadisilate depended on the glucose concentration. These stimulatory effects of aclatonium napadisilate on endocrine and exocrine pancreatic secretion were inhibited by the muscarinic receptor antagonist pirenzepine but were not affected by the cholecystokinin receptor antagonist proglumide. These results indicate that aclatonium napadisilate stimulates both endocrine and exocrine pancreatic secretion via muscarinic receptors and that its action on B cells is more potent than on the exocrine pancreas.