Pirenzepine (LS 519): a weak inhibitor of acid secretion by isolated rat parietal cells

Carbamylcholine-stimulated potentiation of dibutyryl cyclic AMP-induced acid secretion by isolated rat parietal cells was specifically inhibited by the muscarinic cholinergic antagonist pirenzepine at an IC50 of 1.1 microM. In contrast to the weak inhibition by pirenzepine, the potentiation was inhibited by atropine at an IC50 of 4.6 nM. In vivo, pirenzepine is one-tenth as potent as atropine as an inhibitor of acid secretion. The weak activity of pirenzepine shown in this study suggests that its in vivo inhibitory activity is likely due to an interaction with a site involved in the regulation of gastric acid secretion which has higher-affinity muscarinic receptors for pirenzepine than those associated with parietal cells.