MUSCARINIC M(1) RECEPTOR INHIBITION REDUCES GASTRODUODENAL BICARBONATE SECRETION AND PROMOTES GASTRIC PROSTAGLANDIN E(2) SYNTHESIS IN HEALTHY-VOLUNTEERS

The selective muscarinic M(1) receptor antagonist, pirenzepine, consid erably stimulates duodenal mucosal bicarbonate secretion in the rat an d increases gastric luminal release of prostaglandin E(2) (PGE(2)) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion and luminal output of PGE(2) into the stomach an d the duodenum of nine healthy volunteers using a new technique permit ting simultaneous measurements. In the stomach modified sham feeding i ncreased bicarbonate secretion from 382 (62) mu mol/h (mean (SEM)) to 959 (224) mu mol/h (p<0.02). In the duodenum modified sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increase d mucosal bicarbonate secretion from 191 (14) mu mol/cmXh to 266 (27) mu mol/cmXh (p<0.02) and 634 (157) mu mol/cmXh (p<0.01), respectively. Pirenzepine (10 mg/h intravenously) reduced basal and vagally stimula ted gastric and basal duodenal bicarbonate secretion by about 50% (p<0 .03). In the stomach, but not the duodenum, basal and vagally stimulat ed PGE(2) output increased significantly (p<0.05) in response to piren zepine. In conclusion, human gastroduodenal mucosal bicarbonate secret ion is regulated by a pirenzepine sensitive mechanism, which is probab ly cholinergic. The rise in gastric PGE(2) output seen in response to M(1) receptor inhibition by pirenzepine suggests the existence of a fe ed back loop secondary to the decrease seen in bicarbonate secretion.