AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 5 925-G930, Copyright © 1989 by American Physiological Society
Oxygen metabolites modulate prostaglandin E2 production by isolated gastric mucosal cells
C. E. Olson, M. C. Chen, D. A. Amirian and A. H. Soll
Center for Ulcer Research and Education, Wadsworth Veterans Administration Medical Center, Los Angeles, California.
We previously found that the small cell fraction of isolated cells from
canine gastric mucosa is a major producer of prostaglandin E2 (PGE2) and
identified macrophages as the predominant cellular source. Prostaglandin-H
synthase activity is dependent on the continuous presence of
hydroperoxides. Because reactive oxygen metabolites may mediate mucosal
injury in inflammatory or ischemic disease, we studied the release of PGE2
by isolated gastric cells during exposure to an oxygen
metabolite-generating system, xanthine and xanthine oxidase. We found a
concentration-dependent relationship between xanthine oxidase concentration
and PGE2 production without cell lysis. The maximum PGE2 production
stimulated by oxidants was equivalent to the maximum PGE2 response to
bradykinin and A23187. The chief and parietal cell fractions produced very
little PGE2 with xanthine oxidase concentrations that stimulated maximal
PGE2 production in the small cell fraction. Uric acid did not stimulate
PGE2 production. Catalase completely inhibited the response, while
superoxide dismutase had a partial inhibitory effect. Hydrogen peroxide
stimulated concentration-dependent PGE2 production with an ED50 of
approximately 5 microM. We concluded that reactive oxygen metabolites
stimulate PGE2 production by the small cell fraction of gastric mucosa.
