EFFECT OF PF-10040 ON PAF-INDUCED AIRWAY RESPONSES IN NEONATALLY IMMUNIZED RABBITS

1 PF 10040 displaced [H-3]-PAF from binding sites on rabbit platelets with an IC50 = 1.07 x 10(-5) M, which was approximately three orders o f magnitude below that of a standard PAF antagonist WEB 2086 (IC50 = 4 .23 x 10(-9) M). 2 PF 10040 at doses of 5 and 10 mg (direct intratrach eal administration) had no effect on the acute bronchoconstriction ind uced by PAF in neonatally immunized rabbits (airway resistance R(L) or dynamic compliance C-dyn) However, the PAF-induced increase in airway responsiveness to inhaled histamine was significantly inhibited (R(L) and C-dyn) by both doses of PF 10040. 3 PF 10040 (5 and 10 mg) signif icantly inhibited the total pulmonary cell infiltration and neutrophil influx induced by PAF as assessed by bronchoalveolar lavage. PAF-indu ced eosinophil infiltration into the airways was significantly inhibit ed in rabbits that received only 10 mg PF 10040. 4 We suggest from the results of the present study that PF 10040 does not exert an inhibito ry effect on PAF-induced airway responses solely via antagonism of the PAF receptor located on platelets, as PF 10040 significantly inhibite d PAF-induced airway hyperresponsiveness in the absence of an effect o n the acute bronchospasm induced by PAF. 5 We provide further evidence that pulmonary eosinophil infiltration and the development of airway hyperresponsiveness are not causally related events as the lower dose of PF 10040 (5 mg) significantly inhibited PAF-induced airway hyperres ponsiveness yet was without effect on the eosinophil influx.