Mechanism of action of p-chlorobiphenyl on the inhibition of platelet aggregation.
p-Chlorobiphenyl (1-50 microM) concentration-dependently inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 and thrombin. The IC50 values of p-chlorobiphenyl on the arachidonic acid and collagen-induced platelet aggregation were 2.9 +/- 0.5 and 12.8 +/- 2.3 microM, respectively. The formation of both platelet thromboxane B2 and prostaglandin D2 caused by arachidonic acid was inhibited by p-chlorobiphenyl concentration-dependently. In myo-[3H]inositol-labeled and fura-2-loaded platelets. [3H]inositol monophosphate generation and the rise in intracellular Ca2- stimulated by arachidonic acid were inhibited by p-chlorobiphenyl. In human platelet-rich plasma, p-chlorobiphenyl and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate and adrenaline without affecting the primary aggregation. It is concluded that p-chlorobiphenyl may be a cyclo-oxygenase inhibitor and its antiplatelet action is mainly due to the inhibition of thromboxane formation.
Ko
F N
FN
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Yeh
L J
LJ
Liang
H C
HC
Kuo
S C
SC
Teng
C M
CM
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000097:blood; D010743:Phospholipids / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000097:blood; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D001713:Biphenyl Compounds; D010716:Phosphatidylinositols; D010743:Phospholipids; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; C006983:4-chlorobiphenyl; D015230:Prostaglandin D2; D002118:Calcium