title: Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.
abstract: The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.
authors.affiliation: Department of Medical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Mertz-Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Hillingsø
authors.forename: K
authors.initials: K
authors.lastname: Bukhave
authors.forename: J
authors.initials: J
authors.lastname: Rask-Madsen
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007419:Intestinal Secretions / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D011899:Ranitidine; D009853:Omeprazole