RP 59227, a novel PAF receptor antagonist: effects in guinea pig models of airway hyperreactivity.
The PAF antagonists RP 59227 and WEB 2086 (100 micrograms.kg-1 i.v., 10 min prior to platelet-activating factor (PAF) infusion) abolished or reduced (P less than 0.05) hyperreactivity to bombesin measured at 1 h. Similarly, RP 59227 and WEB 2086 (10 mg.kg-1 p.o., 1 h prior to PAF aerosol) abolished or reduced (P less than 0.01) hyperreactivity to bombesin measured at 24 h. Lower concentrations of RP 59227 and WEB 2086 (3 mg.kg-1 p.o.) were without effect. RP 59227 or WEB 2086 (3 or 10 mg.kg-1 p.o., 1 h prior to antigen aerosol) did not protect against antigen-induced hyperreactivity to histamine measured at 24 h. Antigen-(but not PAF)-induced hyperreactivity was accompanied by an increase in total cell number and, specifically, eosinophil number in bronchoalveolar lavage fluid. The PAF antagonists did not affect BALF cell populations. It is concluded that RP 59227 and WEB 2086 are potent PAF antagonists which inhibit PAF-but not antigen-induced airway hyperreactivity. These data suggest that endogenous PAF may not be involved in antigen-induced hyperreactivity in the guinea pig.
Underwood
S L
SL
Rhône-Poulenc Rorer Ltd., Dagenham Research Center, Essex, U.K.
Lewis
S A
SA
Raeburn
D
D
D000818:Animals; D000941:Antigens / Q000276:immunology; D001381:Azepines / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001986:Bronchial Spasm / Q000139:chemically induced / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
D000941:Antigens; D001381:Azepines; D010972:Platelet Activating Factor; D011725:Pyridines; D013844:Thiazoles; D014230:Triazoles; C052518:WEB 2086; C065022:RP 59227; D010047:Ovalbumin