AJP - Gastrointestinal and Liver Physiology, Vol 247, Issue 3 240-G247, Copyright © 1984 by American Physiological Society
Dissociated response of acid and pepsin secretion to omeprazole in an in vitro perfused mouse stomach
C. J. Fimmel, M. M. Berger and A. L. Blum
The effect of omeprazole, an inhibitor of the parietal cell H+-K+-ATPase,
on pepsin and acid secretion was studied in an in vitro perfused whole
mouse stomach model. Omeprazole inhibited basal and dibutyryl cAMP
(DBcAMP)- and histamine-stimulated acid secretion in a dose-dependent
fashion with a maximally effective dose of 10(-4) M. At the same time,
omeprazole induced a dose-dependent increase of unstimulated pepsin
release. This increase was not affected by pretreatment with 10(-3) M
atropine or 10(-4) M cimetidine. It was, however, inhibited by
preincubation with 10(-4) M carbonyl cyanide m-chlorophenylhydrazone
(CCCP). Pepsin secretion after maximally effective doses of histamine or
DBcAMP was not affected by 10(-4) M omeprazole. In a concentration of
10(-5) M, the effect of omeprazole was additive to the effect of submaximal
concentrations of carbachol and histamine. NaSCN and imidazole mimicked the
effect of omeprazole on acid secretion, but pepsin release was only
stimulated with 10(-2) M imidazole. Another weak base, benzylamine,
stimulated acid and pepsin in parallel. Luminal perfusion with solutions of
high K+ concentration did not enhance basal pepsin release. The dissociated
response of acid and pepsin secretion indicates that omeprazole does not
act selectively on the parietal cell. The stimulation of pepsin secretion
might be related to the weak base properties of the compound.
