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Role of leukotrienes and platelet activating factor in acute gastric mucosal lesions in rats.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1989 May 19; Vol. 164 (2), pp. 285-92. - Publication Year :
- 1989
-
Abstract
- Leukotriene C4 (LTC4) and platelet activating-factor (PAF) were found to affect gastric microcirculation and mucosal integrity but their role in acute gastric damage has not been established. The present study with rats confirms that exogenous LTC4 (10 micrograms/kg.h s.c.) or PAF (10 micrograms/kg i.p.) alone caused only mild gastric mucosal injury but greatly augmented mucosal lesions produced by other irritants such as absolute ethanol, taurocholate, aspirin or stress. These acute lesions were accompanied by a significant increase in mucosal generation of LTC4, and the addition of PAF further increased it. Pretreatment with BN 52021, a PAF receptor antagonist, abolished PAF-induced gastric lesions and reduced LTC4 generation in tests with PAF plus ethanol. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, and FPL 55712, an LTC receptor-antagonist, reduced dose dependently the extent of gastric damage in various models of gastric lesions. Again, these protective effects were accompanied by a reduction in mucosal LTC4 formation. In addition, the protection induced by nordihydroguaiaretic acid was reversed in part by the pretreatment with indomethacin, suggesting that it could be attributed to increased biosynthesis of protective PG. The results indicated that LTC4 biosynthesis is increased in various forms of gastric damage and that LTC4 may be involved in the pathogenesis of this damage.
- Subjects :
- Animals
Aspirin pharmacology
Chromones pharmacology
Ethanol pharmacology
Gastric Mucosa metabolism
Ginkgolides
Lactones pharmacology
Male
Masoprocol pharmacology
Rats
Rats, Inbred Strains
SRS-A antagonists & inhibitors
Stress, Psychological physiopathology
Taurocholic Acid pharmacology
Diterpenes
Leukotrienes physiology
Platelet Activating Factor physiology
Stomach Ulcer physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 164
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 2759176
- Full Text :
- https://doi.org/10.1016/0014-2999(89)90469-x