INHIBITION OF PAF-INDUCED PLATELET-AGGREGATION BY WEB-2086 IN-VITRO, AN ANTAGONIST TO THE RECEPTOR FOR PLATELET-ACTIVATING-FACTOR, IN BOVINE

The sensitivity of bovine platelet aggregation in response to PAF stim ulation and the ability of WEB 2086 (a thieno-triazolodiazepine) to in hibit response to PAF-induced platelet aggregation were investigated i n the blood from five healthy male Belgian Blue calves. The recorded r esponse to PAF showed a plateau which was dependent on the PAF concent ration. Platelet aggregation induced by PAF consists of two mechanisms : reversible and irreversible aggregations which are accompanied by th e release of platelet granule contents. Reversible aggregation occurre d above (2 . 10(-9) mol/l) PAF, and irreversible aggregation occurred above (2 . 10(-7) mol/l) PAF. Addition of WEB 2086 to bovine platelets in vitro induced a rightward shift in the dose-response curve to PAF. WEB 2086 inhibited PAF-induced aggregation in a competitive reversibl e manner (pA(2) = 7.61). The results of our study show that PAF induce s platelet aggregation in platelet-rich plasma (PRP) and that addition of WEB 2086 to bovine platelets in vitro inhibits PAF-induced Platele t Aggregation.