THE MODULATORY EFFECT OF ANTIGEN-INDUCED AND PAF-INDUCED ASTHMATIC REACTION BY AEROSOL ADMINISTRATION OF OKY-046 IN GUINEA-PIGS

The therapeutic effect of a thromboxane A2 (TXA2) synthetase inhibiter on asthma is still controversial. This study was aimed at clarifying its effect on asthmatic reactions in guinea pigs, Both ovalbumin (OVA) - and platelet activating factor (PAF)-induced dual phase airway spasm and hyperreactivity in guinea pigs were used as the asthma model. Our results demonstrated that aerosol administration of OKY-046 could inh ibit both OVA- and PAF-induced late phase bronchoconstriction and airw ay hyperreactivity to methacholine in OVA sensitized guinea pigs. PAF administration could also induced dual phase bronchoconstriction in no rmal guinea pigs, Similarly, late phase airway spasm and airway hyperr eactivity after PAF exposure was also blocked by OKY-046. In conclusio n, aerosol administration of OKY-046 is a safe and effective way to mo dulate OVA- and PAF-induced asthmatic reactions. The protective effect of OKY-046 on OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity indicates that TXA2 might play an important ro le in the late phase asthmatic reaction and airway hyperreactivity. Th e normalization of PAF-induced airway hyperreactivity by OKY-046 also indicates that PAF induced airway inflammation might be through the ge neration of TXA2.