The modulatory effect of antigen- and PAF-induced asthmatic reaction by aerosol administration of OKY-046 in guinea pigs.
The therapeutic effect of a thromboxane A2 (TXA2) synthetase inhibitor 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 inhibit both OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity to methacholine in OVA sensitized guinea pigs. PAF administration could also induced dual phase bronchoconstriction in normal guinea pigs. Similarly, late phase airway spasm and airway hyperreactivity after PAF exposure was also blocked by OKY-046. In conclusion, aerosol administration of OKY-046 is a safe and effective way to modulate 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 role in the late phase asthmatic reaction and airway hyperreactivity. The normalization of PAF-induced airway hyperreactivity by OKY-046 also indicates that PAF induced airway inflammation might be through the generation of TXA2.
Tsai
J J
JJ
Section of Allergy and Clinical Immunology, Cathay General Hospital-Taipei, Taiwan.
Tsai
C F
CF
Wang
S R
SR
Han
S H
SH
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000627:therapeutic use*; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D010047:Ovalbumin; D010972:Platelet Activating Factor; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013997:Time Factors
D006633:Histamine Antagonists; D008689:Methacrylates; D010972:Platelet Activating Factor; D010047:Ovalbumin; D013930:Thromboxane-A Synthase; C034364:ozagrel