Pirenzepine inhibits pancreatic exocrine secretion in the rat

Pirenzepine is a newly developed anticholinergic drug that reduces gastric acid secretion and is therefore used in Europe and Japan to treat patients with peptic ulcer. The inhibitory effect of pirenzepine on pancreatic exocrine function and its reversibility were studied in the isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine caused a concentration-dependent rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion without altering the maximal increase. Addition of 10 microM pirenzepine at the beginning as well as after 10 or 20 min of stimulation with 1 microM carbamylcholine rapidly abolished pancreatic secretions in both the isolated acini and isolated perfused pancreas. The inhibitory effect of pirenzepine was fully reversible in the isolated acini, whereas pirenzepine caused a small residual inhibition on pancreatic exocrine secretion in the isolated perfused pancreas. These results suggest the existence of pirenzepine-sensitive receptors in the pancreatic vagal pathway at a site remote from the acinar cell. The present data indicate that pirenzepine may have an influence on pancreatic exocrine function by inhibiting not only acinar cell cholinergic receptor but also endogenous cholinergic activity of the pancreas when a large dose is given.