Adenylate cyclase activity in gastric mucosal biopsies and cAMP in gastric juice before and after cimetidine treatment in healthy subjects

Abstract

Previous studies have revealed augmented parietal call sensitivity to histamine stimulation after cessation of cimetidine treatment in healthy subjects. To elucidate one possible mechanism for this effect, we measured cAMP in gastric mucosa and gastric juice during histamine stimulation in vivo and histamine-stimulated adenylate cyclase activity in vitro in biopsy material obtained by gastroscopy. In eight healthy subjects the cAMP content of gastric corpus mucosal biopsies was measured before, during, and after infusion of 2.5 and 25.6 microgram . kg-1 . h-1 of histamine dihydrochloride. No increase in cAMP content was found. In 10 healthy subjects cAMP secretion into gastric juice was studied before and 36 to 84 h after cessation of 4 weeks' treatment with cimetidine, 1 g/day. No significant increase of cAMP output was found in response to infusion of 2.5 and 25.6 microgram . kg-1 . h-1 of histamine dihydrochloride either before or after the treatment period. Thus histamine does not stimulate cAMP secretion into gastric juice in man. In the same 10 subjects histamine-stimulated adenylate cyclase activity was studied in vitro in biopsy material obtained before and 60 h after cessation of cimetidine treatment. The dose-response curve of the adenylate cyclase activity was not shifted to the left. The results indicate that the augmented parietal cell sensitivity to histamine, seen after stopping cimetidine treatment in healthy subjects, is not due to increased sensitivity of the adenylate cyclase-cAMP system to histamine stimulation.