The possible role of LTC4 in the pathogenesis of ethanol-induced gastric lesions in mice and their prevention by 5-lipoxygenase inhibitor AA-861, and leukotriene receptor antagonist FPL-55712.

The extent of acute gastric lesions produced by intragastric administration of ethanol in mice paralleled gastric leukotriene (LT) C4 levels. Furthermore, an inverse dose-response relationship was observed between the extent of gastric lesions and the number of mast cells in the gastric mucosa. When mice were pretreated with the 5-lipoxygenase inhibitor, AA-861, both the extent of ethanol-induced gastric lesions and the level of gastric LTC4 decreased dose-dependently. In contrast, when mice were pretreated with the LTC4 receptor antagonist, FPL-55712, the extent of ethanol-induced gastric lesions was depressed without significant reduction of gastric LTC4 level. These results indicate that both production of LTC4 and also subsequent binding of LTC4 to the receptors is important for the pathogenesis of gastric lesions and suggest that mast cell-derived LTC4 plays a major role in the development of ethanol-induced gastric lesions.