Cells were isolated from human gastric mucosa on a large scale from gastric resection specimens and on a microscale from endoscopic biopsies by sequential incubations with pronase and collagenase. The accumulation of aminopyrine (AP) was used as an index of acid production in the parietal cells. Basal accumulation was about 0.2 pmol AP/10(4) parietal cells. Addition of histamine, db-cAMP, pentagastrin and carbachol increased the aminopyrine accumulation. Maximal accumulation was of the order of 1000-2800% of the control and was obtained after stimulation by 10(-4) M histamine and by 10(-3) M db-cAMP. Stimulation by pentagastrin and by carbachol reached 200 to 350% of the control. EC50 was 2 X 10(-6) M for histamine, 10(-8) M for pentagastrin, and 4 X 10(-6) M for carbachol. Human parietal cells were enriched from a mixture of gastric mucosal cells by isopycnic centrifugation on density gradients of Percoll. A parietal cell fraction with a purity of 83% was obtained. The density of human parietal cells was estimated to 1.06 g . ml-1.
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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