Oxygen metabolites modulate prostaglandin E2 production by isolated gastric mucosal cells.
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.
Olson
C E
CE
Center for Ulcer Research and Education, Wadsworth Veterans Administration Medical Center, Los Angeles, California.
Chen
M C
MC
Amirian
D A
DA
Soll
A H
AH
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D010100:Oxygen / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D014527:Uric Acid; D000001:Calcimycin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D015232:Dinoprostone; D010100:Oxygen; D001920:Bradykinin