Relationship of omeprazole-induced hypergastrinemia to gastric pH

The increase in gastrin caused by the gastric proton pump inhibitor, omeprazole, is presumably secondary to inhibition of gastric acid secretion but could also be due to a direct effect on the gastrin cells. This experiment was designed to determine whether gastrin elevations caused by omeprazole are related to intragastric pH. We studied gastrin release and acid output in response to 10% peptone broth (400 ml) in five dogs with gastric fistulas. The broth, at pH 5.5 or 2.5, was instilled into the stomach through the cannula, and the desired pH was maintained by intragastric titration with 0.1N NaHCO3 for 2 hours. Studies at each pH level were performed on separate days before, during, and after omeprazole (10 mumol/kg daily for 20 days). Omeprazole increased intragastric pH to greater than or equal to 3.5 for 24 hours. At pH 5.5 omeprazole inhibited acid secretion and increased gastrin levels; however, setting the intragastric pH at 2.5 completely blocked omeprazole's effect on gastrin release. Therefore these data support the hypothesis that the hypergastrinemia caused by omeprazole is dependent on gastric pH and gastric acid suppression.