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. 1985 Oct;86(2):439–446. doi: 10.1111/j.1476-5381.1985.tb08913.x

Increased metabolism of arachidonic acid in an immune model of colitis in guinea-pigs.

N K Boughton-Smith, B J Whittle
PMCID: PMC1916693  PMID: 3931734

Abstract

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.

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Selected References

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  1. BICKS R. O., BROWN G., HICKEY H. D., Jr, ROSENBERG E. W. FURTHER OBSERVATIONS ON A DELAYED HYPERSENSITIVITY REACTION IN THE GUINEA PIG COLON. Gastroenterology. 1965 Apr;48:425–429. [PubMed] [Google Scholar]
  2. Borgeat P., Hamberg M., Samuelsson B. Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases. J Biol Chem. 1976 Dec 25;251(24):7816–7820. [PubMed] [Google Scholar]
  3. Boughton-Smith N. K., Hawkey C. J., Whittle B. J. Biosynthesis of lipoxygenase and cyclo-oxygenase products from [14C]-arachidonic acid by human colonic mucosa. Gut. 1983 Dec;24(12):1176–1182. doi: 10.1136/gut.24.12.1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gould S. R. Assay of prostaglandin-like substances in faeces and their measurement in ulcerative colitis. Prostaglandins. 1976 Mar;11(3):489–497. doi: 10.1016/0090-6980(76)90095-2. [DOI] [PubMed] [Google Scholar]
  5. Gould S. R., Brash A. R., Conolly M. E., Lennard-Jones J. E. Studies of prostaglandins and sulphasalazine in ulcerative colitis. Prostaglandins Med. 1981 Feb;6(2):165–182. doi: 10.1016/0161-4630(81)90088-4. [DOI] [PubMed] [Google Scholar]
  6. Higgs G. A., Vane J. R. Inhibition of cyclo-oxygenase and lipoxygenase. Br Med Bull. 1983 Jul;39(3):265–270. doi: 10.1093/oxfordjournals.bmb.a071831. [DOI] [PubMed] [Google Scholar]
  7. Hoult J. R., Moore P. K., Marcus A. J., Watt J. On the effect of sulphasalazine on the prostaglandin system and the defective prostaglandin inactivation observed in experimental ulcerative colitis. Agents Actions Suppl. 1979;(4):232–244. [PubMed] [Google Scholar]
  8. Kirsner J. B., Shorter R. G. Recent developments in "nonspecific" inflammatory bowel disease (first of two parts). N Engl J Med. 1982 Apr 1;306(13):775–785. doi: 10.1056/NEJM198204013061304. [DOI] [PubMed] [Google Scholar]
  9. Kirsner J. B., Shorter R. G. Recent developments in nonspecific inflammatory bowel disease (second of two parts). N Engl J Med. 1982 Apr 8;306(14):837–848. doi: 10.1056/NEJM198204083061404. [DOI] [PubMed] [Google Scholar]
  10. Ligumsky M., Karmeli F., Sharon P., Zor U., Cohen F., Rachmilewitz D. Enhanced thromboxane A2 and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalazine. Gastroenterology. 1981 Sep;81(3):444–449. [PubMed] [Google Scholar]
  11. Norris A. A., Lewis A. J., Zeitlin I. J. Actions of anticolitic drugs on a guinea-pig model of immune colitis. Agents Actions. 1982 Apr;12(1-2):239–242. doi: 10.1007/BF01965153. [DOI] [PubMed] [Google Scholar]
  12. Norris A. A., Lewis A. J., Zeitlin I. J. Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis. Agents Actions. 1982 Apr;12(1-2):243–246. doi: 10.1007/BF01965154. [DOI] [PubMed] [Google Scholar]
  13. Rampton D. S., Sladen G. E., Youlten L. J. Rectal mucosal prostaglandin E2 release and its relation to disease activity, electrical potential difference, and treatment in ulcerative colitis. Gut. 1980 Jul;21(7):591–596. doi: 10.1136/gut.21.7.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Randall R. W., Eakins K. E., Higgs G. A., Salmon J. A., Tateson J. E. Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C. Agents Actions. 1980 Dec;10(6):553–555. doi: 10.1007/BF02024164. [DOI] [PubMed] [Google Scholar]
  15. Salmon J. A. A radioimmunoassay for 6-keto-prostaglandin F1alpha. Prostaglandins. 1978 Mar;15(3):383–397. doi: 10.1016/0090-6980(78)90122-3. [DOI] [PubMed] [Google Scholar]
  16. Salmon J. A., Simmons P. M., Palmer R. M. A radioimmunoassay for leukotriene B4. Prostaglandins. 1982 Aug;24(2):225–235. doi: 10.1016/0090-6980(82)90148-4. [DOI] [PubMed] [Google Scholar]
  17. Sharon P., Stenson W. F. Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology. 1984 Mar;86(3):453–460. [PubMed] [Google Scholar]
  18. Sharon P., Stenson W. F. Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease. Gastroenterology. 1985 Jan;88(1 Pt 1):55–63. doi: 10.1016/s0016-5085(85)80132-3. [DOI] [PubMed] [Google Scholar]
  19. Siegel M. I., McConnell R. T., Cuatrecasas P. Aspirin-like drugs interfere with arachidonate metabolism by inhibition of the 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3774–3778. doi: 10.1073/pnas.76.8.3774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Siegel M. I., McConnell R. T., Porter N. A., Selph J. L., Truax J. F., Vinegar R., Cuatrecasas P. Aspirin-like drugs inhibit arachidonic acid metabolism via lipoxygenase and cyclo-oxygenase in rat neutrophils from carrageenan pleural exudates. Biochem Biophys Res Commun. 1980 Jan 29;92(2):688–695. doi: 10.1016/0006-291x(80)90388-5. [DOI] [PubMed] [Google Scholar]
  21. Turner S. R., Tainer J. A., Lynn W. S. Biogenesis of chemotactic molecules by the arachidonate lipoxygenase system of platelets. Nature. 1975 Oct 23;257(5528):680–681. doi: 10.1038/257680a0. [DOI] [PubMed] [Google Scholar]
  22. Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  23. Wölbling R. H., Aehringhaus U., Peskar B. A., Morgenroth K., Peskar B. M. Release of slow-reacting substance of anaphylaxis and leukotriene C4-like immunoreactivity from guinea pig colonic tissue. Prostaglandins. 1983 Jun;25(6):809–822. doi: 10.1016/0090-6980(83)90005-9. [DOI] [PubMed] [Google Scholar]

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