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Exaggerated prostaglandin production by colonic smooth muscle in rabbit colitis

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Abstract

Enhanced production of arachidonic acid metabolites by colonic mucosa has been reported in ulcerative colitis as well as in experimental models of colitis. However, production of these compounds by colonic smooth muscle from colitis subjects has not been described. To evaluate arachidonic acid metabolism in colonic tissue, we studied the production of prostaglandin E2 (PGE2) by mucosa and muscularis propria in two experimental models of acute colitis in which inflammation was virtually confined to the mucosa. Colitis was induced in New Zealand white rabbits by either of two methods, dinitrochlorobenzene (DNCB) sensitization or formalin followed by intravenous soluble immune complexes (F-IC). Arachidonic acid metabolites were identified from in vitro incubations of tissue with [14C]arachidonic acid by thin layer chromatography followed by autoradiography. The major eicosanoid metabolites of colitis mucosa and muscularis were14C-labeled prostaglandin E2, prostaglandin F2a and 6-keto prostaglandin f1a. PGE2 was quantitated from incubations without labeled arachidonic acid by radioimmunoassay. PGE2, expressed as picograms per milligram protein per 20 min (mean±sem), was increased in F-IC mucosa (1093±141 vs 645±189, P < 0.05) and DNCB mucosa (1354±487 vs 527±222, P < 0.05) compared to normals. PGE2 production by uninflamed colitis muscularis propria was also increased five-to eightfold compared to normals for F-IC muscularis (1594±329 vs 189±35, P < 0.005) and DNCB muscularis (1287±171 vs 225±72, P < 0.005). Thus, the adjacent inflammation in colonic mucosa may induce increased eicosanoid production by the uninflamed smooth muscle. Increased PGE2, in turn, may contribute to the smooth muscle dysfunction seen in colitis.

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References

  1. Rampton DS, Sladen GE, Bhakoo KK, Heinzelmann DI, Youlten LJF: Rectal mucosal prostaglandin E release and electrolyte transport in ulcerative colitis. Adv Prostaglandin Thromboxane Res 8:1621–1625, 1980

    PubMed  Google Scholar 

  2. Racusen LC, Binder HJ: Effect of prostaglandin on ion transport across isolated colonic mucosa. Dig Dis Sci 25:900–904, 1980

    PubMed  Google Scholar 

  3. Kimber DV, Field M, Johnson J, Henderson A, Gershon E: Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and postaglandins. J Clin Invest 50:1218–1230, 1971

    PubMed  Google Scholar 

  4. Sanger GJ, Bennett A: Regional differences in the responses to prostanoids of circular muscle from guinea-pig isolated intestine. J Pharm Pharmacol 32:755–708, 1980

    Google Scholar 

  5. Vanasin B, Greenough W, Schuster MM: Effect of prostaglandin (PG) on electrical and motor activity of isolated colonic muscle. Gastroenterology 58:1004, 1970 (abstract)

    Google Scholar 

  6. Hunt RH, Dilawari JB, Misiewicz JJ: The effect of intravenous prostaglandin F2a and E2 on the motility of the sigmoid colon. Gut 16:47–49, 1975

    PubMed  Google Scholar 

  7. Spriggs EA, Code CF, Bargen JA, Curtiss RK, Hightower NC Jr: Motility of the pelvic colon and rectum of normal persons and patients with ulcerative colitis. Gastroenterology 19:480–491, 1951

    PubMed  Google Scholar 

  8. Kern F, Jr, Almy TP, Abbot FK, Bogdonoff MD: The motility of the distal colon in nonspecific ulcerative colitis. Gastroenterology 19:492–503, 1951

    PubMed  Google Scholar 

  9. Snape WJ Jr, Matarazzo SA, Cohen S: Abnormal gastrocolonic response in patients with ulcerative colitis. Gut 21:392–396, 1980

    PubMed  Google Scholar 

  10. Gould SR: Assay of prostaglandin-like substances in faeces and their measurement in ulcerative colitis. Prostaglandins 11:489–497, 1976

    PubMed  Google Scholar 

  11. Gould SR, Brash AR, Conolly ME, Lennard-Jones JE: Studies of prostaglandins and sulphasalazine in ulcerative colitis. Prostaglandins Med 6:165–182, 1981

    PubMed  Google Scholar 

  12. Sharon P, Ligumsky M, Rachmilewitz D, Zor U: Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology 75:638–640, 1978

    PubMed  Google Scholar 

  13. Rampton DS, Sladen GE, Youlten LJF: Rectal mucosal prostaglandin E2 release and its relation to disease activity, electrical potential difference and treatment in ulcerative colitis. Gut 21:591–596, 1980

    PubMed  Google Scholar 

  14. Smith PR, Dawson DJ, Swan CHJ: Prostaglandin synthetase activity in acute ulcerative colitis: Effects of treatment with sulphasalazine, codeine phosphate and prednisolone. Gut 20:802–805, 1979

    PubMed  Google Scholar 

  15. Harris DW, Smith PR, Swan CHJ: Determination of prostaglandin synthetase activity in rectal biopsy material and its significance in colonic disease. Gut 19:875–877, 1978

    PubMed  Google Scholar 

  16. 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 81:444–449, 1981

    PubMed  Google Scholar 

  17. Boughton-Smith NK, Hawkey CJ, Whittle BJR: Biosynthesis of lipoxygenase and cyclooxygenase products from [14C]-arachidonic acid by human colonic mucosa. Gut 24:1176–1182, 1983

    PubMed  Google Scholar 

  18. Bennett A, Hensby CN, Sanger GJ, Stamford IF: Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers. Br J Pharmacol 74:435–444, 1981

    PubMed  Google Scholar 

  19. Sanders KM, Northrup TE: Prostaglandin synthesis by microsomes of circular and longitudinal gastrointestinal muscles. Am J Physiol 244:G442-G448, 1983

    PubMed  Google Scholar 

  20. LeDuc LE, Needleman P: Regional localization of prostacyclin and thromboxane synthesis in dog stomach and intestinal tract. J Pharmacol Exp Ther 211:181–188, 1979

    PubMed  Google Scholar 

  21. Rabin BS, Rogers SJ: A cell-mediated immune model of inflammatory bowel disease in the rabbit. Gastroenterology 75:29–33, 1978

    PubMed  Google Scholar 

  22. Hodgson HJF, Potter BJ, Skinner J, Jewell DP: Immunecomplex mediated colitis in rabbits. An experimental model. Gut 19:225–232, 1978

    PubMed  Google Scholar 

  23. McCluskey ER, Corr PB, Lee BI, Saffitz JE, Needleman P: The arachidonic acid metabolic capacity of canine myocardium is increased during healing of acute myocardial infarction. Circ Res 51:743–750, 1982

    PubMed  Google Scholar 

  24. Danon A, Chang LCT, Sweetman BJ, Nies AS, Oates JA: Synthesis of prostaglandins by the rat renal papillain vitro. Biochim Biophysica Acta 388:71–83, 1975

    Google Scholar 

  25. Gornall AG, Bardawill CJ, David MM: Determination of serum proteins by means of biuret reaction. J Biol Chem 177:751–766, 1949

    Google Scholar 

  26. Zipser RD, Myers S, Needleman P: Stimulation of renal prostaglandin synthesis by the pressor activity of vasopressin. Endocrinology 108:495–199, 1981

    PubMed  Google Scholar 

  27. Palmadessa DJ, Schwartz SE, Bedrick A, Starr CM: Prostaglandin (PG) synthesis in an animal model of inflammatory bowel disease. Gastroenterology 84:1269, 1983 (abstract)

    Google Scholar 

  28. Sharon P, Stenson WF: Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease. Gastroenterology 88:55–63, 1985

    PubMed  Google Scholar 

  29. Zipser RD, Patterson JB, Kao HW, Hauser CJ, Locke R: Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis. Am J Physiol 249:G457-G463, 1985

    PubMed  Google Scholar 

  30. Lands WEM: The biosynthesis and metabolism of prostaglandins. Annu Rev Physiol 41:633–652, 1979

    PubMed  Google Scholar 

  31. Piper P, Vane JR: The release of prostaglandins from lung and other tissues. Ann NY Acad Sci 180:363–385, 1971

    PubMed  Google Scholar 

  32. Zifroni A, Treves AJ, Sachar DB, Rachmilewitz D: Prostanoid synthesis by cultured intestinal epithelial and mononuclear cells in inflammatory bowel disease. Gut 24:659–664, 1983

    PubMed  Google Scholar 

  33. Clark JG, Kostal KM, Marino BA: Bleomycin-induced pulmonary fibrosis in hamsters: An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production. J Clin Invest 72:2082–2091, 1983

    PubMed  Google Scholar 

  34. Okegawa T, Jones PE, DeSchryver K, Kawasaki A, Needleman P: Metabolic and cellular alterations underlying the exaggerated renal prostaglandin and thromboxane synthesis in ureter obstruction in rabbits: Inflammatory response involving fibroblasts and mononuclear cells. J Clin Invest 71:81–90, 1983

    PubMed  Google Scholar 

  35. Dayer JM, Bread J, Chess L, Krane SM: Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells. J Clin Invest 64:1386–1392, 1979

    PubMed  Google Scholar 

  36. Dinarello CA: Interleukin-1. Rev Infect Dis 6:51–95, 1984

    PubMed  Google Scholar 

  37. Dayer J-M, de Rochemonteix B, Burrus B, Demczuk S, Dinarello CA: Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J Clin Invest 77:645–648, 1986

    PubMed  Google Scholar 

  38. Baracos V, Rodemann HP, Dinarello CA, Goldberg AL: Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1). N Engl J Med 308:553–558, 1983

    PubMed  Google Scholar 

  39. Albrightson CR, Baenziger NL, Needleman P: Exaggerated human vascular cell prostaglandin biosynthesis mediated by mpnocytes: Role of monokines and interleukin 1. J Immunol 135:1972–1977, 1985

    Google Scholar 

  40. Cohen JD, Kao HW, Tan ST, Lechago J, Snape WJ Jr: Effect of acute experimental colitis on rabbit colonic smooth muscle. Am J Physiol 251:G538-G545, 1986

    PubMed  Google Scholar 

  41. Zipser RD, Nast CC, Lee M, Kao HW, Duke R:In vivo production of leukotriene B4 and leukotriene C4 in rabbit colitis. Relationship to inflammation. Gastroenterology 92:33–39, 1987

    PubMed  Google Scholar 

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This work was supported by the National Institutes of Health through BRSG RR-05551, by the National Foundation for Ileitis & Colitis, and by the James L. Stamps Foundation, Inc.

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Kao, H.W., Zipser, R.D. Exaggerated prostaglandin production by colonic smooth muscle in rabbit colitis. Digest Dis Sci 33, 697–704 (1988). https://doi.org/10.1007/BF01540433

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  • DOI: https://doi.org/10.1007/BF01540433

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