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Identification and Distribution of Arachidonic Acid Metabolites in the Human Gastrointestinal Tract, and the Ways in Which Some of these Affect the Longitudinal Muscle

  • Alan Bennet
  • Christopher N. Hensby
  • Gareth J. Sanger
  • Ian F. Stamford
Part of the NATO Advanced Study Institutes Series book series

Abstract

Prostaglandins (PGs) may have various roles in gastrointestinal function. They have also been implicated as contributors to various gastrointestinal diseases, including gastritis, gastric ulcer formation, ulcerative colitis, irritable bowel syndrome, idiopathic intestinal pseudo-obstruction, food intolerance, and radiation-induced and other forms of diarrhoea (1–8). In contrast, PGs administered as drugs may be useful in the treatment of peptic ulceration, prevention of aspirin- or indomethacin-induced gastric mucosal damage (9) and reversal of post-operative ileus (10). Knowledge of the types of compounds formed from the C20-unsaturated fatty acids eicosatrienoic, eicosatetraenoic (arachidonic) and eicosapentaenoic acids, and their actions on the human gut, is therefore important. Most studies to date have concerned PGE and PGFα compounds, but we have now extended this to include other metabolites of arachidonic acid.

Keywords

Arachidonic Acid Irritable Bowel Syndrome Terminal Ileum Longitudinal Muscle Krebs Solution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    H. O. J. Collier. Prostaglandin synthetase inhibitors and the gut. In: Prostaglandin Synthetase Inhibitors. H. J. Robinson and J. R. Vane, eds., pp. 121–133, Raven Press, New York (1974).Google Scholar
  2. 2.
    A. T. Mennie, V. Dalley, L. C. Dinneen and H. O. J. Collier. Treatment of radiation-induced gastrointestinal distress with acetylsalicylate. Lancet, 2: 942–943 (1975).PubMedCrossRefGoogle Scholar
  3. 3.
    J. R. Luderer, L. M. Demers, E. M. Bonnem, A. Saleem and G. H. Jeffries. Elevated prostaglandin E in idopathic intestinal pseudo obstruction. New England J. Med., 295: 1179 (1976).CrossRefGoogle Scholar
  4. 4.
    S. R. Gould, A. R. Brash and M. E. Conolly. Increased prostaglandin production in ulcerative colitis. Lancet, 2: 198 (1977).Google Scholar
  5. 5.
    W. Schlegel, K. Wenk, H. C. Dollinger and S. Raptis. Concentrations of prostaglandin A-, E- and F-like substances in gastric mucosa of normal subjects and of patients with various gastric diseases. Clin. Sci. Mol. Med., 52: 255–258 (1977).PubMedGoogle Scholar
  6. 6.
    P. D. Buisseret, L. J. F. Youlten, D. I. Heinzelmann and M. H. Lessof. Prostaglandin-synthesis inhibitors in prophylaxis of food intolerance. Lancet, 1: 906–908 (1978).PubMedCrossRefGoogle Scholar
  7. 7.
    D. W. Harris, P. R. Smith nd C. H. J. Swan. Determination of prostaglandin synthetase activity in rectal biopsy material and its significance in colonic disease. Gut, 19: 875–877 (1978).PubMedCrossRefGoogle Scholar
  8. 8.
    J. Rask-Madsen and K. Bukhave. Indomethacin-responsive diarrhoea in irritable bowel syndrome. Gut, 19: A448 (1978).Google Scholar
  9. 9.
    M. M. Cohen and J. M. Pollett. Prostaglandin E2 prevents aspirin and indomethacin damage to human gastric mucosa. Surg. Forum., 27: 400–401 (1976).PubMedGoogle Scholar
  10. 10.
    M. J. Ruwart, M. S. Klepper and B. D. Rush. The beneficial effects of prostaglandins in post-operative ileus. Gastroenterology, 74: 1088 (1978).Google Scholar
  11. 11.
    A. Bennett, J. G. Murray and J. H. Wyllie. Occurrence of prostaglandin E2 in the human stomach, and a study of its effects on human isolated gastric muscle. Br. J. Pharmac., 32: 339–349 (1968).Google Scholar
  12. 12.
    A. Bennett, I. F. Stamford and H. L. Stockley. Estimation and characterization of prostaglandins in the human gastrointestinal tract. Br. J. Pharmac., 61: 579–586 (1977).CrossRefGoogle Scholar
  13. 13.
    C. Pace-Asciak and L. S. Wolfe. A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates. Biochemistry, N.Y., 10: 3657–3664 (1971).CrossRefGoogle Scholar
  14. 14.
    C. Pace-Asciak. Isolation, structure and biosynthesis of 6-keto prostaglandin Flα in the rat stomach. Am. Chem. Soc., 98: 2348–2349 (1976).CrossRefGoogle Scholar
  15. 15.
    M. Ali, J. Zamecnik, A. L. Cerskus, A. J. Stoessl, W. H. Barnett and J. W. D. McDonald. Synthesis of thromboxane B2 and prostaglandins by bovine gastric mucosal microsomes. Prostaglandins, 14: 819–827 (1977).PubMedGoogle Scholar
  16. 16.
    S. Moncada, J. A. Salmon, J. R. Vane and B. J. R. Whittle. Formation of prostacyclin and its product 6-oxo-PGFia by the gastric mucosa of several species. J. Physiol., 275: 4P (1978).Google Scholar
  17. 17.
    H. Sinzinger, K. Silberbauer, M. Winter and H. Seyfried. Human rectal mucosa generates prostacyclin. Lancet, 2: 1253 (1978).PubMedCrossRefGoogle Scholar
  18. 18.
    W. G. Unger, I. F. Stamford and A. Bennett. Extraction of prostaglandins from human blood. Nature, Lond., 233: 336–337 (1971).CrossRefGoogle Scholar
  19. 19.
    A. Bennett, I. F. Stamford and W. G. Unger. Prostaglandin E2 and gastric acid secretion in man. J.Physiol., 229: 349–360 (1973).PubMedGoogle Scholar
  20. 20.
    I. F. Stamford and W. G. Unger. Improved purification and chromatography of extracts containing prostaglandins. J. Physiol., 225: 4–5P (1972).Google Scholar
  21. 21.
    K. Green and B. Samuelsson. Thin layer chromatography of prostaglandins. J. Lipids Res., 5: 117–120 (1964).Google Scholar
  22. 22.
    N. H. Anderson. Preparative thin layer and column chromatography of prostaglandins. J. Lipid Res., 10: 316–319 (1969).Google Scholar
  23. 23.
    B. M. Peskar, A. Holland and B. A. Peskar. Quantitative determination of prostaglandins in human gastric juice by radioimmunoassay. Clin. Chem. Acta., 55: 21–27 (1974).CrossRefGoogle Scholar
  24. 24.
    B. A. Peskar, U. Schade, E. Rietschel and B. M. Peskar. Synthesis and metabolism of endogenous prostaglandins by human gastric mucosa. Abstr. Fourth. Int. Prostaglandin Conference, Washington, p. 93 (1979).Google Scholar
  25. 25.
    A. Bennett, K. G. Eley and G. B. Scholes. Effects of prostaglandins El and E2 on human, guinea-pig and rat small intestine. Br. J. Pharmac., 34: 639–647 (1968).CrossRefGoogle Scholar
  26. 26.
    A. Bennett and B. Fleshier. Prostaglandins and the gastrointestinal tract. Gastroenterology, 59: 790–800 (1970).PubMedGoogle Scholar
  27. 27.
    B. Fleshier and A. Bennett. Responses of human, guinea-pig and rat colonic circular muscle to prostaglandins. J. Lab. Clin. Med., 74: 872 (1969).Google Scholar
  28. 28.
    A. Bennett and J. Posner. Studies on prostaglandins antagonists. Br. J. Pharmac., 42: 584–594 (1971).CrossRefGoogle Scholar
  29. 29.
    A. Bennett and H. L. Stockley. The contribution of prostaglandins in the muscle of human isolated small intestine to neurogenic responses. Br. J. Pharmac., 61: 573–578 (1977).CrossRefGoogle Scholar
  30. 30.
    C. Omini, S. Moncada and J. R. Vane. The effects of prostacyclin (PGI2) on tissues which detect prostaglandins (PGs). Prostaglandins, 14: 625–632 (1977).PubMedGoogle Scholar
  31. 31.
    B. J. R. Whittle, K. G. Mugridge and S. Moncada. Use of the rabbit transverse stomach strip to identify and assay prostacyclin, PGA2, PGD2 and other prostaglandins. Eur. J. Pharmac., 53: 167–172 (1979).CrossRefGoogle Scholar
  32. 32.
    N. Gilmore, J. R. Vane and J. H. Wyllie. Prostaglandins released by the spleen. Nature, 218: 1135–1140 (1968).PubMedCrossRefGoogle Scholar
  33. 33.
    A. Bennett and H. L. Stockley. The intrinsic innervation of the human alimentary tract and its relation to function. Gut, 16: 443–453 (1975).PubMedCrossRefGoogle Scholar
  34. 34.
    J. P. Hughes, P. J. Kadowitz, A. L. Hyman, J. E. Ray and P. D. Joiner. Pharmacology of human isolated colonic circular and longitudinal smooth muscle from cancer and non-cancer patients. Dis. Col. Rect., 19: 120–125 (1976).CrossRefGoogle Scholar
  35. 35.
    A. Bennett and G. J. Sanger. Prostacyclin relaxes the longitudinal muscle of human isolated stomach and antagonizes contractions to some prostanoids. J. Physiol., (in press) (1979).Google Scholar
  36. 36.
    A. Bennett and G. J. Sanger. Prostacyclin and prostaglandin E2 selectively antagonize responses of human isolated myometrium to excitatory prostaglandins. J. Physiol., 292: 36–37P (1979).Google Scholar
  37. 37.
    C. Malmsten. Some biological effects of prostaglandin endoperoxide analogues. Life. Sci., 18: 169–176 (1977).CrossRefGoogle Scholar
  38. 38.
    R. A. Coleman, P. P. A. Humphrey, I. Kennedy, G. P. Levy and P. Lumley. U-46619, a selective thromboxane A2-like agonist? Br. J. Pharmac., (in press) (1979).Google Scholar
  39. 39.
    H. L. Stockley and A. Bennett. Modulation of activity by prostaglandins in human gastrointestinal muscle. In: Fifth International Symposium on Gastrointestinal Motility. G. Vantrappen, ed., Typoff Press, Belgium, pp. 31–36 (1976).Google Scholar
  40. 40.
    A. Bennett, D. Pratt and G. J. Sanger. Antagonism by fenamates of prostaglandin action in guinea-pig and human alimentary muscle. Br. J. Pharmac., (in press) (1979).Google Scholar
  41. 41.
    D. E. Burleigh. The effects of indomethacin on the tone and spontaneous activity of the human small intestine in vitro. Arch. Int. Pharmacodyn. Ther., 225: 240–245 (1977).Google Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Alan Bennet
    • 1
    • 2
  • Christopher N. Hensby
    • 1
    • 2
  • Gareth J. Sanger
    • 1
    • 2
  • Ian F. Stamford
    • 1
    • 2
  1. 1.Department of SurgeryKing’s College Hospital Medical SchoolLondonEngland
  2. 2.Department of Clinical PharmacologyRoyal Postgraduate Medical SchoolLondonEngland

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