LEUKOTRIENES DO NOT CONTRIBUTE TO THE PATHOGENESIS OF INDOMETHACIN-INDUCED ULCERATION OF THE GASTRIC ANTRUM IN THE RE-FED RAT

The potential involvement of leukotrienes in the pathogenesis of indom ethacin-induced ulceration of the rat gastric antrum has been studied. Pretreatment with the leukotriene biosynthesis inhibitor, MK886 (30 m g/kg p.o.), inhibited the increases in blood and antral leukotriene B- 4 release ex vivo associated with the evolution of antral ulceration. Despite this, however, there was no significant reduction in either th e area of antral ulceration, or in the associated blood neutrophilia a nd neutrophil infiltration into the gastric antrum. Similarly, pretrea tment with the leukotriene B-4 antagonist, SC41930 (50 mg/kg p.o.) or the peptidyl leukotriene antagonist ICI198,615 (50 mg/kg p.o.) did not inhibit the area of antral ulceration induced by indomethacin. Thus, in contrast to published reports studying fundic ulceration, our resul ts suggest that leukotrienes do not play a major role either in the pa thogenesis of indomethacin-induced ulceration of the rat gastric antru m or neutrophil infiltration into the damaged antrum.