Digestive Diseases and Sciences

, Volume 30, Supplement 11, pp 105S–108S | Cite as

Prostaglandins in pathophysiology of peptic ulcer disease

  • S. J. Konturek
Part 3: Role of Prostaglandins in Mucosal Cytoprotection in Health and Disease


Gastric ulcer (GU) and duodenal ulcer (DU) occur as a result of the imbalance between aggressive and defensive factors affecting the gastroduodenal mucosa. Prostaglandins (PG) of E and I series are generated throughout the gastrointestinal tract, particularly in the gastric and duodenal mucosa, and are released into the gut lumen upon vagal and hormonal stimulation. Endogenous PGs may be involved in the maintenance of mucosal integrity, control of mucosal blood flow and protection against potentially noxious agents. Gastric mucosa of ulcer patients tends to generate smaller amounts of PGs of E and I series and exhibits a reduced ratio of PG to thromboxane generation, which suggests that the deficiency of protective PG may play a role in the pathogenesis of peptic ulcer. Suppression of mucosal generation of PGs by non-steroidal anti-inflammatory compounds causes mucosal damage and increases the risk of the formation or exacerbation of peptic ulcer. Exogenous PGE and its stable analogs have been tested successfully in the treatment of GU and DU and the results so far obtained indicate that these agents significantly increase the ulcer healing rate. Certain anti-ulcer drugs such as carbenoxolone, sucralfate, colloidal bismuth and cimetidine appear to exert their beneficial effects on ulcer healing by mediating the release of endogenous PGs.


  1. 1.
    Le Duc LE, Needleman P: Regional localization of prostacyclin and thromboxane synthesis in dog stomach and intestinal tract. J Pharmacol Exp Ther 211:181–188, 1977Google Scholar
  2. 2.
    Peskar BM, Seyberth HW, Peskar BA: Synthesis and metabolism of prostaglandins by human gastric mucosa.In Advances in Prostaglandins and Thromboxane Research, vol 7, B Samuelsson, PW Ramwell, R Paoletti (eds). New York, Raven Press, 1980, pp 151–154Google Scholar
  3. 3.
    Konturek SJ, Obtulowicz W, Sito E, Oleksy J, Wilkon S, Dembinska-Kiec A: Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients. Gut 22:283–289, 1981Google Scholar
  4. 4.
    Sharon P, Zifroni A, Ligumsky M, Cohen F, Karmeli F, Rachmilewitz D: Prostanoid synthesis by cultured gastric and duodenal mucosa: Role in the pathogenesis of duodenal ulcer. Scand J Gastroenterol 18:1045–1049, 1983Google Scholar
  5. 5.
    Bennett A, Stamford IF, Unger WG: Prostaglandin E2 and gastric acid secretion in man. J Physiol (Lond) 229:349–360, 1973Google Scholar
  6. 6.
    Baker R, Jaffe BM, Venables CW: Endogenous prostaglandins in peptic ulcer disease. Gut 20:294–299, 1979Google Scholar
  7. 7.
    Hinsdale JG, Engel JJ, Wilson DE: Prostaglandin E2 in peptic ulcer disease. Prostaglandins 6:459–500, 1974Google Scholar
  8. 8.
    Konturek SJ, Kwiecien N, Obtulowicz W, Oleksy J, Sito E, Kopp B: Prostaglandins in peptic ulcer disease: Effect of non-steroidal anti-inflammatory compounds (NOSAC). Scand J Gastroenterol 19 (Suppl 92):250–253, 1983Google Scholar
  9. 9.
    Wright JP, Young GO, Klaff JJ, Wears LA, Price SK, Marks IN: Gastric mucosal prostaglandin E levels in patients with gastric ulcer disease and carcinoma. Gastroenterology 82:263–267, 1982Google Scholar
  10. 10.
    Hillier K, Smith CL, Jewell R: Abnormal duodenal mucosa (DM) prostanoid and thromboxane synthesis in duodenal ulcer (DU) patients. IUPHAR 9th Intern Congress Pharmacol, London 1984, pp 160Google Scholar
  11. 11.
    Konturek SJ: Gastric cytoprotection. Mt Sinai J Med 49:355–369, 1982Google Scholar
  12. 12.
    Whittle BJR: Cellular mediators in gastric damage: Actions of thromboxane A2 and its inhibitors.In Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, A Allen, G Flemström, A Garner, W Silen, LA Turnberg (eds). New York, Raven Press, 1984 pp 295–300Google Scholar
  13. 13.
    Alquist DA, Dozois RR, Zinsmeister AR, Malagelada JR: Duodenal prostaglandin synthesis and acid loads in health and in duodenal ulcer disease. Gastroenterology 85:522–528, 1983Google Scholar
  14. 14.
    Rainsford KD, Velo G: Side-effects of Anti-inflammatory Analgesic Drugs, vol 6. New York, Raven Press, 1984, pp 306Google Scholar
  15. 15.
    Konturek SJ, Kwiecien N, Obtulowicz W, Dembinska-Kiec A, Polanski M, Kopp B, Sito E, Oleksy J: Effect of carprofen and indomethacin on gastric function, mucosal integrity and generation of prostaglandin in men. Hepatogastroenterology 29:267–270, 1982Google Scholar
  16. 16.
    Konturek SJ, Obtulowicz W, Kwiecien N, Oleksy J: Generation of prostaglandins in gastric mucosa of patients with peptic ulcer disease. Effect of non-steroidal anti-inflammatory compounds. Scand J Gastroenterol 19 (Suppl 101):75–77, 1984Google Scholar
  17. 17.
    Ritchie WP, Shearburn EW: Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. Gastroenterology 73:62–65, 1977Google Scholar
  18. 18.
    Kivilaakso E, Fromm D, Silen W: Relationship between ulceration and intramural pH of gastric mucosa during hemorrhagic shock. Surgery 84:70–76, 1978Google Scholar
  19. 19.
    Cohen MM, Cheung, G, Lyster DM: Prevention of aspirin-induced fecal blood loss by prostaglandin E2. Gut 21:602–606, 1980Google Scholar
  20. 20.
    Johansson C, Kollberg B, Nordeman R: Protective effect of prostaglandin E2 in the gastrointestinal tract during indomethacin treatment of rheumatic diseases. Gastroenterology 78:479–493, 1980Google Scholar
  21. 21.
    Gilbert DA, Surowicz CM, Silverstein FE, Weinberg CR, Saunders DR, Feld AD, Sanford RL, Bergman D, Washington P: Prevention of acute aspirin-induced gastric mucosal injury by 15-R-15 methyl prostaglandin E2: An endoscopic study. Gastroenterology 86:339–345 1984Google Scholar
  22. 22.
    Konturek SJ, Kwiecien N, Obtulowicz W, Dembinska-Kiec A, Oleksy J: Role of endogenous prostaglandin in peptic ulcer disease.In Gut Peptides and Ulcer, A Myoshi (ed). Tokyo, Biomed Res Found, 1982, pp 429–433Google Scholar
  23. 23.
    Fung WP, Karim SMM: Effect of prostaglandin E2 on the healing of gastric ulcer: a double blind endoscopic trial. Aust NZ J Med 6:121–122, 1976Google Scholar
  24. 24.
    Gibinski K, Rybicka J, Mikos E, Nowak A: Double blind clinical trial on gastroduodenal ulcer healing with prostaglandin E2 analogues. Gut 18:636–639, 1977Google Scholar
  25. 25.
    Vantrappen G, Janssens J, Popiela T: Effect of 15-R-15 methyl prostaglandin E2 (Arbaprostil) on the healing of duodenal ulcer: A double-blind multicenter study. Gastroenterology 83:357–363, 1982Google Scholar
  26. 26.
    Kollberg B, Slezak P: The effect of prostaglandin E2 on duodenal ulcer healing. Prostaglandins 24:527–536, 1982Google Scholar
  27. 27.
    Peskar BM: Effect of carbenoxolone on prostaglandin synthesizing and metabolizing enzymes and correlation with gastric mucosal carbenoxolone concentrations. Scand J Gastroenterol 15 (Suppl):109–112, 1980Google Scholar
  28. 28.
    Hollander D, Tarnawski A, Gergeley H, Zipser RD: Sucralfate protection of the gastric mucosa against ethanol-induced injury: A prostaglandin-mediated process? Scand J Gastroenterol 19(Suppl 101):97–102, 1984Google Scholar
  29. 29.
    Tarnawski A, Hollander D, Cumming D, Krause WJ, Gergeley H, Zipser RD: Are antacids neutralizers only? Histologic, ultrastructural and functional changes in normal gastric mucosa induced by antacids. Gastroenterology 86:1276, 1984Google Scholar
  30. 30.
    Branski D, Sharon P, Karmeli F, Rachmilewitz D: Effect of cimetidine on human gastric and duodenal ulcer prostanoid synthesis. Scand J Gastroenterol 19:457–460, 1984Google Scholar

Copyright information

© Plenum Publishing Corporation 1985

Authors and Affiliations

  • S. J. Konturek
    • 1
  1. 1.Institute of PhysiologyAcademy of MedicineKrakowPoland

Personalised recommendations