A method to simultaneously investigate histamine-induced cyclic AMP and aminopyrine accumulation in isolated gastric mucosal cells from human biopsies.

A method has been developed to simultaneously measure two parameters of histamine-induced gastric secretion, cyclic AMP and aminopyrine accumulation, in gastric mucosal cells from human biopsies. Histamine stimulated cyclic AMP and aminopyrine accumulation with different time courses. Cyclic AMP production reached a maximum at 30 min, whereas maximal aminopyrine accumulation was obtained after the cells had been incubated for 90 min in presence of 100 mcM histamine. Histamine was more potent in stimulating aminopyrine than cyclic AMP accumulation. The ED50 values for histamine-induced aminopyrine accumulation were estimated to be 0.88 +/- 0.02 and 25.53 +/- 8.75 mcM for cyclic AMP production, respectively. The aminopyrine accumulation was more than half-maximally increased at 1 mcM histamine without significant effects on the cyclic AMP basal level. It remains to be elucidated whether this finding indicates, besides cyclic AMP, the involvement of calcium in histamine stimulus. The histamine H2-receptor antagonists cimetidine and ranitidine inhibited both in vitro parameters, whereas the gastric proton pump inhibitor omeprazole only affected aminopyrine accumulation. Our method might be a valuable tool for in vitro pharmacological and clinical investigations on histamine-induced gastric secretion in human biopsies.