Effect of YM264 on the airway hyperresponsiveness and the late asthmatic response in a guinea pig model of asthma.
We investigated the effects of YM264, a specific platelet-activating factor (PAF) antagonist, on the airway hyperresponsiveness (AH) and the late asthmatic response (LAR) of guinea pigs that were sensitized by exposure to aerosolized ovalbumin (OA). Respiratory resistance (Rrs) was determined by the oscillation technique. Airway responsiveness was evaluated by administering a dose of histamine at which the Rrs reached 200% of the baseline value (H200). Animals were administered 1 or 3 mg/kg of YM264 orally 30 min before and again at 3 h after exposure to OA. YM264 significantly suppressed AH 24 h after and 5 days after the exposure. YM264 also suppressed the development of the LAR and accumulation of eosinophils and neutrophils in the tracheal mucosa of guinea pigs. These observations suggest that PAF is involved in the AH and the development of the LAR in asthma. PAF antagonists may play a beneficial role in the treatment of asthma.
Arima
M
M
Department of Allergy and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan.
Yukawa
T
T
Makino
S
S
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007114:Immunization / Q000379:methods; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D010879:Piperazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D013997:Time Factors; D014132:Trachea / Q000473:pathology
D000336:Aerosols; D010879:Piperazines; D010972:Platelet Activating Factor; D013844:Thiazoles; D053778:Thiazolidines; C068679:YM 264; D010047:Ovalbumin