Mertz-Nielsen A, Hillingsø J, Bukhave K, Rask-Madsen J
Department of Medical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Denmark.
Gut. 1996 Jan;38(1):6-10. doi: 10.1136/gut.38.1.6.
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.
质子泵抑制剂奥美拉唑意外地导致十二指肠近端黏膜碳酸氢盐分泌率高于先前使用H2受体拮抗剂抑制胃酸时所报道的水平。对健康志愿者进行胃十二指肠灌注，以评估这一偶然发现是由奥美拉唑更强的胃酸抑制作用所致，还是可能由不同的药物作用方式引起。在对照实验（n = 17）以及分别用高剂量奥美拉唑（n = 17）和雷尼替丁（n = 9）预处理后，通过一种允许同时测量的技术，在同一受试者中测量基础状态和刺激状态下胃和十二指肠的碳酸氢盐分泌率。通过返滴定法测量各自流出液中的碳酸氢盐浓度。奥美拉唑和雷尼替丁均完全抑制胃酸分泌（pH 6.9对6.8；p>0.05）。与对照实验相比，奥美拉唑导致基础状态（均值（标准误））（597（48）对351（39）μmol/h；p<0.02）和迷走神经刺激状态下（834（72）对474（66）μmol/h；p<0.02）十二指肠碳酸氢盐分泌率更高，但在酸刺激状态下（3351（678）对2550（456）μmol/h；p>0.05）则不然。此外，奥美拉唑和雷尼替丁联合使用可增加（p = 0.05）十二指肠碳酸氢盐分泌，而单独使用雷尼替丁对基础或刺激状态下的分泌均无影响。在胃中，基础状态以及迷走神经刺激状态下的碳酸氢盐分泌与胃酸抑制方式无关。这些结果表明，质子泵抑制剂奥美拉唑促进十二指肠近端黏膜碳酸氢盐分泌，显然与其胃酸抑制作用无关。其作用机制仍属推测。
