INHIBITORY EFFECT OF DS-4574, A PEPTIDOLEUKOTRIENE ANTAGONIST WITH MAST-CELL STABILIZING ACTION, ON COMPOUND 48 80-INDUCED GASTRIC-MUCOSAL LESIONS IN RATS/

We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene an tagonist with mast cell stabilizing action, on rat gastric mucosal les ions induced by compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of disodium cromoglycate (DSCG: a mast cell stab ilizer), LY171883 (a peptidoleukotriene antagonist) and cimetidine (a histamine H, receptor antagonist). Subcutaneous administration of C48/ 80 (1 mg/kg) once daily for four consecutive days produced extensive g astric lesions in the fundic mucosa. DS-4574 (20, 50 and 100 mg/kg/day , oral) and DSCG (200 mg/kg/day, intraperitoneal) treatment markedly i nhibited formation of these mucosal lesions, but LY171883 (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did n ot. Moreover, DS4574 and DSCG significantly suppressed both hyperhista minemia and histamine release from rat peritoneal mast cells induced b y C48/80. These results indicate that the inhibitory effect of DS-4574 on gastric lesions induced by C48/80 may be related to its mast cell stabilizing action, but to neither its antisecretory nor its peptidole ukotriene antagonistic activity.