Increased metabolism of arachidonic acid in an immune model of colitis in guinea-pigs.
Inflammation of the guinea-pig colon was produced by skin sensitization and subsequent intracolonic challenge with the chemical hapten, dinitrochlorobenzene. Metabolism of [14C]-arachidonic acid by homogenates of control colon was very low, although metabolites co-migrating on thin layer chromatography (t.l.c.) with prostaglandin E2 (PGE2), PGF2 alpha, PGD2, 6-keto-PGF1 alpha, thromboxane B2 (TXB2), HHT and 11-, 12-, 15-HETE were formed. There was an overall 3 fold increase in metabolism of [14C]-arachidonic acid by homogenates of inflamed mucosa. The greatest increase in metabolite formation was of PGE2, with smaller increases in HHT, 11-, 12-, 15-HETE, PGD2, TXB2, PGF2 alpha and 6-keto-PGF1 alpha. The formation of these metabolites was inhibited both by indomethacin and the dual pathway inhibitor, BW755C. The formation of immunoreactive PGE2, TXB2 and 6-keto-PGF1 alpha was also increased in homogenates of inflamed guinea-pig colon. The small level of immunoreactive LTB4 detected in control colon was not changed in inflamed colonic tissue. The dinitrochlorobenzene model of colitis offers a means of studying arachidonic acid metabolism in an immune-mediated inflammatory response in intestinal tissue.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D004137:Dinitrochlorobenzene; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011863:Radioimmunoassay
D001095:Arachidonic Acids; D004137:Dinitrochlorobenzene; D011453:Prostaglandins; D011720:Pyrazoles; D016718:Arachidonic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D007213:Indomethacin