Treatment with proton pump inhibitors induces tolerance to histamine-2 receptor antagonists in Helicobacter pylori-negative patients

Background: Treatment with H-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) induces hypergastrinemia and causes rebound hypersecreti on of gastric acid after treatment, and during treatment with H2RAs toleran ce develops. In the present study we investigated whether a treatment perio d with a PPI induced tolerance to an H(2)RA. Methods: Thirteen patients wit h esophagitis were given omeprazole for 90 days. Twenty-four-hour pH monito rings without and with ranitidine were performed before and after treatment with omeprazole. Blood samples and biopsy specimens from the oxyntic mucos a were analyzed for gastrin, histamine, and chromogranin A. Results: An inc rease in mucosal histamine and a reduction in the effect of ranitidine on g astric pH was found 14 days after discontinuing omeprazole compared with be fore treatment in Helicobacter pylori-negative but not in H. pylori-positiv e patients. Conclusions: Treatment with omeprazole reduces the effect of ra nitidine in H. pylori-negative patients. This is caused by an increase in h istamine released by the enterochromaffin-like cell secondarily to hypergas trinemia, corresponding to the tolerance towards H2RAs seen in patients wit h Zollinger-Ellison syndrome.