INTERFERENCE OF THE PAF RECEPTOR ANTAGONIST, PCA-4248, WITH THE RAT PLEURISY EVOKED BY INFLAMMATORY MEDIATORS OR ALLERGEN

This study investigated the effect of the platelet-activating factor ( PAF) receptor antagonist, PCA 4248, on the rat pleurisy caused by PAF, serotonin, bradykinin, histamine or allergen. The pleurisy was assess ed by measuring liquid extravasation and leucocyte infiltration. Oral pretreatment with PCA 4248 (2.5-20 mg/kg) completely inhibited the ple ural exudation caused by intrathoracic (i.t.) injection of PAF (1 mug/ cavity) (ED50 = 6.1 mg/kg), partially (42% reduction) the one induced by serotonin (100 mug/cavity), but was inactive against histamine (200 mug/cavity) or bradykinin (50 mug/cavity). PCA 4248 blocked the incre ase in the number of neutrophils, eosinophils and mononuclear cells ob served 6 h after the i.t. injection of PAF, as well as the selective e osinophil accumulation noted 24 h later. In actively sensitized rats, PCA 4248 (20 mg/kg) failed to modify the increase in the total leucocy te counts noted 4 h after ovalbumin (12 mug/cavity), but dose dependen tly inhibited the pleural exudation observed within 1 h and the late e osinophil infiltration noted 24 h post-antigen. These observations led us to suggest that PCA 4248 is a potent PAF antagonist with anti-sero toninergic properties. Its interference with exudation and eosinophil infiltration caused by allergen is consistent with the interpretation that PCA 4248 may be useful in the management of allergic dysfunctions .