Abstract
The antisecretory properties of omeprazole, cimetidine, and ranitidine were studied in vitro, using human gastric mucosal cells, which were obtained by sequential pronase and collagenase incubation of small tissue specimens obtained by endoscopic biopsy. Acid production was measured as the accumulation of radioactive aminopyrine in the acid compartments of the parietal cells. Acid production was stimulated via H2-receptors by histamine (10(-4) M or 5 X 10(-6) M) and via intracellular mechanisms by db-cAMP (10(-3) M). Omeprazole induced a dose-dependent inhibition of acid production for all stimulators (IC50 = 2 X 10(-7) M and 3 X 10(-8) M with high and low concentrations of histamine, respectively, and 5 X 10(-6) M with db-cAMP). The H2-receptor antagonists dose-dependently inhibited the histamine-stimulated acid production (IC50 for cimetidine = 10(-5) M and 10(-6) M and for ranitidine = 10(-5) M and 2 X 10(-7) M for high and low concentrations of histamine, respectively). Neither cimetidine nor ranitidine inhibited acid production after intracellular stimulation with db-cAMP. Omeprazole reduced the aminopyrine accumulation stimulated by histamine (10(-4) M) already within 5-10 min, whereas cimetidine (10(-3) M and ranitidine (10(-4) M) required 20-30 min. The unstimulated level of acid production was also inhibited by omeprazole but not by the H2-receptor antagonists.
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