Role of Leukotrienes in Experimental Gastric Ulceration

  • B. M. Peskar
  • E. Bacha
  • P. Nowak
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 177)


Gastric mucosal damage induced by topical irritants such as ethanol, strong acid or strong base are preceded by severe disturbances of the gastric mucosal microcirculation resulting in a decrease in mucosal blood flow, vascular stasis, marked engorgement of microvessels and leakage of plasma proteins and blood cells.1,2 Gastroprotective compounds such as prostaglandins (PG) prevent the microcirculatory changes caused by the irritants.1.2 The cysteinyl leukotrienes (LT) LTC4 and LTD4 infused into the arterial supply of the rat stomach cause a rapid and marked decrease in vascular flow rate.3,4 Furthermore, LTC4, but not LTD4, has been found to induce sluggish blood flow and stasis in the rat gastric submucosal microcirculation closely resembling the effects of topical irritants.5 Finally, both LTC4and LTD4, although not ulcerogenic themselves, potentiate the noxious effects of gastric irritants.6,7


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    P. H. Guth, G. Paulsen, and H. Nagata, Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: effect of prostaglandin cytoprotection, Gastroenterology 87: 1083 (1984).Google Scholar
  2. 2.
    G. Pihan,D. Majzoubi, C. Haudenschild, J. S. Trier, and S. Szabo, Early microcirculytory stasis in acute gastric mucosal injury in the rat and prevention by 16,16 dimethyl prostaglandin E2 or sodium thiosuslfat Gastroenterology 91: 1415 (1986).CrossRefGoogle Scholar
  3. 3.
    A. Dembinska-Kiec, B. A. Peskar, M. K. Müller, and B. M.Peskar, The effect of platelet-activating factor on flow rate and eicosanoid release in the isolated perfused rat gastric vascular bed. Prostaglandins, in press.Google Scholar
  4. 4.
    B. M. Peskar, Cysteinyl leukotrienes in experimental ulcers in rats, in: Leukotrienes and Prostanoids in Health and Disease, U. Zor, Z. Naor, A. Danon, eds., Karger, Basel, in press.Google Scholar
  5. 5.
    B. J. R. Whittle, N. Oren-Wolman, and P. H. Guth, Gastric va-soconstrictor actions of leukotriene C4, PGF2a, and throm-boxane mimetic U-46619 on rat submucosal microcirculation in vivo. Am. J. Physiol. 248: 580 (1985).Google Scholar
  6. 6.
    G. Pihan, C. Rogers, and S. Szabo, Vascular injury in acute gastric mucosal damage. Mediatory role of leukotrienes. Dig. Dis. Sci. 33: 625 (1988).CrossRefGoogle Scholar
  7. 7.
    S. J. Konturek, T. Brzozowski, D. Drozdowicz, and G. Beck, Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet-activating factor and stress in rats. Dig. Dis. Sci. 33: 806 (1988).CrossRefGoogle Scholar
  8. 8.
    B. M. Peskar, K. Lange, U. Hoppe, et al: Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. Prostaglandins 31: 283 (1986).CrossRefGoogle Scholar
  9. 9.
    K. Lange, B. A. Peskar, and B. M. Peskar, Stimulation of rat gastric mucosal leukotriene C4 formation by ethanol and ef-fect of gastric protective drugs, Adv. Prostaglandin, Thromboxane, and Leukotriene Res. 17: 299, (1987).Google Scholar
  10. 10.
    B. M. Peskar and K. Lange, Role of leukotriene C4 in gastric protection by sulfhy dryl-modulating agents and metals in the rat. Gastroenterology 92: 1573 (1987).Google Scholar
  11. 11.
    A. Robert, Gastric cytoprotection by sodium salicylate,Prostaglandins 21 (Suppl.): 139 (1981).PubMedGoogle Scholar
  12. 12.
    B. M. Peskar, U. Hoppe, K. Lange, and B. M. Peskar, Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C4 and prostanoid release: relation to ethanol-induced injury. Br. J. Pharmacol. 93: 937 (1988).CrossRefGoogle Scholar
  13. 13.
    R. J. Bonney, K. Hand, E. E. Opas, B. Olson, A. Dollob, L. W. Argenbright, and J. L. Humes, L-651,896, a novel dual inhi- bitor of prostaglandin and leukotriene synthesis that posesses potent topical anti-inflammatory and analgesic activity. Clin. Res. 34: 739A (1986).Google Scholar
  14. 14.
    J. L. Wallace, P. L. Beck, and G. P. Morris: Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? Am. J. Physiol. 245: G117 (1988).Google Scholar
  15. 15.
    N. K. Boughton-Smith and B. J. R. Whittle, Failure of the in-hibition of rat gastric mucosal 5-lipoxygenase by novel acetohydroxamic acids to prevent ethanol-induced damage. Br. J. Pharmac. 95: 155 (1988).CrossRefGoogle Scholar
  16. 16.
    A. C. Rosam, J. L. Wallace, and B. J. R. Whittle, Potent ulce-rogenic actions of platelet-activating factor on the stomach. Nature 319: 54 (1986).CrossRefGoogle Scholar
  17. 17.
    F. Gonzalez-Crussi and W. Hsueh, Experimental model of ische- mic bowel necrosis. The role of platelet-activating factor and endotoxin. Am.J. Pathol. 112: 127 (1983).PubMedPubMedCentralGoogle Scholar
  18. 18.
    W. Hsueh, F. Gonzalez-Crussi, and J. L. Arroyave, Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor. J. Clin. Invest. 78: 108 (1986)CrossRefGoogle Scholar
  19. 19.
    G. Gillard, A. W. Ford-Hutchinson, C. Chan, S. Charleson, D. Denis, A. Foster, R. Fortion, S. Leger, C. S. McFarlane, H. Morton, H. Piechuta, D. Riendau, C. A. Rouzer, J. Rokach, and R. Young, L-663,536 (3-[3-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylin dol-2-yl)-2, 2-dimethylpropanoic acid) a novel, orally active leukotriene biosynthesis inhibitor, Can. Phvsiol. Pharmacol., in press.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • B. M. Peskar
    • 1
  • E. Bacha
    • 1
  • P. Nowak
    • 1
  1. 1.Department of Experimental Clinical MedicineRuhr-University of BochumBochumGermany

Personalised recommendations