MECHANISM OF ACTION OF P-CHLOROBIPHENYL ON THE INHIBITION OF PLATELET-AGGREGATION

p-Chlorobiphenyl (1-50 mu M) concentration-dependently inhibited the a ggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activ ating factor (PAF), U46619 and thrombin. The IC50 values of p-chlorobi phenyl on the arachidonic acid and collagen-induced platelet aggregati on were 2.9 +/- 0.5 and 12.8 +/- 2.3 mu M, respectively. The formation of both platelet thromboxane B-2 and prostaglandin D-2 caused by arac hidonic acid was inhibited by p-chlorobiphenyl concentration-dependent ly. In myo-[H-3]inositol-labeled and fura-2-loaded platelets, [H-3]ino sitol monophosphate generation and the rise in intracellular Ca2+ stim ulated by arachidonic acid were inhibited by p-chlorobiphenyl. In huma n platelet-rich plasma, p-chlorobiphenyl and indomethacin prevented th e secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate and adrenaline without affecting the prim ary aggregation. It is concluded that p-chlorobiphenyl may be a cyclo- oxygenase inhibitor and its antiplatelet action is mainly due to the i nhibition of thromboxane formation.