Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers.
The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion and luminal output of PGE2 into the stomach and the duodenum of nine healthy volunteers using a new technique permitting simultaneous measurements. In the stomach modified sham feeding increased bicarbonate secretion from 382 (62) mumol/h (mean (SEM)) to 959 (224) mumol/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 increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p < 0.02) and 634 (157) mumol/cm x h (p < 0.01), respectively. Pirenzepine (10 mg/h intravenously) reduced basal and vagally stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p < 0.03). In the stomach, but not the duodenum, basal and vagally stimulated PGE2 output increased significantly (p < 0.05) in response to pirenzepine. In conclusion, human gastroduodenal mucosal bicarbonate secretion is regulated by a pirenzepine sensitive mechanism, which is probably cholinergic. The rise in gastric PGE2 output seen in response to M1 receptor inhibition by pirenzepine suggests the existence of a feed back loop secondary to the decrease seen in bicarbonate secretion.
Mertz-Nielsen
A
A
Department of Medical Gastroenterology, Hvidovre Hospital, Denmark.
Hillingsø
J
J
Eskerod
O
O
Bukhave
K
K
Rask-Madsen
J
J
D000328:Adult; D001639:Bicarbonates / Q000378:metabolism; D003864:Depression, Chemical; D015232:Dinoprostone / Q000096:biosynthesis*; D004386:Duodenum / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013997:Time Factors
D001639:Bicarbonates; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D015232:Dinoprostone