MECHANISMS INVOLVED IN THE ANTIPLATELET ACTIVITY OF TETRAMETHYLPYRAZINE IN HUMAN PLATELETS

Tetramethylpyrazine is the active ingredient of a Chinese herbal medic ine. In this study, tetramethylpyrazine was tested for its antiplatele t activities in human platelet suspensions. In human platelets, tetram ethylpyrazine (0.5-1.5 mM) dose-dependently inhibited both platelet ag gregation and ATP-release reaction induced by a variety of agonists (i .e., ADP, collagen, and U46619). Tetramethylpyrazine (0.5 mM) did not significantly change the fluorescence of platelet membranes labeled wi th diphenylhexatriene, even at the high concentration (1.5 mM). Furthe rmore, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited [H- 3]inositol monophosphate formation stimulated by collagen (5 mu Lg/ml) in [H-3]myoinositol loaded platelets. Tetramethylpyrazine (0.5-1.5 mM ) also dose-dependently inhibited the intracellular free Ca+2 rise of Fura 2-AM loaded platelets stimulated by collagen (5 mu g/ml). Moreove r, tetramethylpyrazine (0.5-1.5 mM) inhibited thromboxane B-2 formatio n stimulated by collagen. At a higher concentration (1.0 mM), tetramet hylpyrazine has also been shown to influence the binding of FITC-trifl avin to platelet glycoprotein IIb/IIIa complex. Triflavin, a specific glycoprotein IIb/IIIa complex antagonist purified from Trimeresurus fl avoviridis venom. It is concluded that the antiplatelet activity of te tramethylpyrazine may possibly involve two pathways: 1) at a lower con centration (0.5 mM), tetramethylpyrazine is shown to inhibit phosphoin ositide breakdown and thromboxane A(2) formation; and 2) at a higher c oncentration (1.0 mM), it leads to the inhibition of platelet aggregat ion through binding to the glycoprotein IIb/IIIa complex. (C) 1998 Els evier Science Ltd.