We investigated the effects of Y 20811 on chemical mediator-induced bronchoconstriction and the release of chemical mediators into lung perfusion fluid during arachidonic acid (AA) -induced bronchoconstriction in guinea pigs. Y-20811(0.01 ?? 1 mg/kg, i.v.), like acetylsalicylic acid or indomethacin, dose-dependently suppressed arachidonic acid and LTD
4-induced bronchoconstriction, and it (1 mg/kg, i.v.) also inhibited PAF-induced bronchoconstriction in guinea pigs. However, at a dose of 1 mg/kg, i.v., it was inactive against the bronchoconstriction induced by histamine, serotonin and acetylcholine in guinea pigs. Y-20811 (0.3 ?? 10 mg/kg) administered orally also prevented the LTD4-induced bronchoconstriction in a dose-dependent manner. This protective effect of Y-20811 (10 mg/kg, p.o.) persisted for at least 24 hr. Y-20811 (10 mg/kg, p.o.) also inhibited antigen-induced bronchoconstriction in guinea pigs passively sensitized with anti-ovalbumin guinea pig serum and pretreated with mepyramine. In the perfused and ventilated guinea pig lungs, Y-20811 inhibited AA-induced bronchoconstriction, decreased the release of TXA
2 (estimated as TXB
2) and increased the release of PGE
2 into the perfused lung fluid, significantly (TXB
2 and PGE
2 were measured by HPLC). Therefore, Y-20811 suppressed various stimulant-induced bronchoconstrictions through the decrease of TXA
2 production and the increase of PGE
2 production. Thus, Y-20811 should prove useful as an antiasthmatic drug.
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