TY - JOUR
T1 - Mechanisms involved in the antiplatelet activity of tetramethylpyrazine in human platelets
AU - Sheu, Joen Rong
AU - Kan, Ya Chen
AU - Hung, Wei Chun
AU - Ko, Wun-Chang
AU - Yen, Mao Hsiung
PY - 1997/11/1
Y1 - 1997/11/1
N2 - Tetramethylpyrazine is the active ingredient of a Chinese herbal medicine. In this study, tetramethylpyrazine was tested for its antiplatelet activities in human platelet suspensions. In human platelets, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited both platelet aggregation 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 with diphenylhexatriene, even at the high concentration (1.5 mM). Furthermore, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited [3H]inositol monophosprate formation stimulated by collagen (5 μg/ml) in [3H]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 μg/ml). Moreover, tetramethylpyrazine (0.5-1.5 mM) inhibited thromboxane B2 formation stimulated by collagen. At a higher concentration (1.0 mM), tetramethylpyrazine has also been shown to influence the binding of FITC-triflavin to platelet glycoprotein IIb/IIIa complex. Triflavin, a specific glycoprotein IIb/IIIa complex antagonist purified from Trimeresurus flavoviridis venom. It is concluded that the antiplatelet activity of tetramethylpyrazine may possibly involve two pathways: 1) at a lower concentration (0.5 mM), tetramethylpyrazine is shown to inhibit phosphoinositide breakdown and thromboxane A2 formation; and 2) at a higher concentration (1.0 mM), it leads to the inhibition of platelet aggregation through binding to the glycoprotein IIb/IIIa complex.
AB - Tetramethylpyrazine is the active ingredient of a Chinese herbal medicine. In this study, tetramethylpyrazine was tested for its antiplatelet activities in human platelet suspensions. In human platelets, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited both platelet aggregation 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 with diphenylhexatriene, even at the high concentration (1.5 mM). Furthermore, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited [3H]inositol monophosprate formation stimulated by collagen (5 μg/ml) in [3H]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 μg/ml). Moreover, tetramethylpyrazine (0.5-1.5 mM) inhibited thromboxane B2 formation stimulated by collagen. At a higher concentration (1.0 mM), tetramethylpyrazine has also been shown to influence the binding of FITC-triflavin to platelet glycoprotein IIb/IIIa complex. Triflavin, a specific glycoprotein IIb/IIIa complex antagonist purified from Trimeresurus flavoviridis venom. It is concluded that the antiplatelet activity of tetramethylpyrazine may possibly involve two pathways: 1) at a lower concentration (0.5 mM), tetramethylpyrazine is shown to inhibit phosphoinositide breakdown and thromboxane A2 formation; and 2) at a higher concentration (1.0 mM), it leads to the inhibition of platelet aggregation through binding to the glycoprotein IIb/IIIa complex.
KW - Glycoprotein IIb/IIIa complex
KW - Intracellular calcium
KW - Platelet aggregation
KW - TMPZ
KW - Thromboxane A
UR - http://www.scopus.com/inward/record.url?scp=0031277778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031277778&partnerID=8YFLogxK
U2 - 10.1016/S0049-3848(97)00253-3
DO - 10.1016/S0049-3848(97)00253-3
M3 - Article
C2 - 9526946
AN - SCOPUS:0031277778
SN - 0049-3848
VL - 88
SP - 259
EP - 270
JO - Thrombosis Research
JF - Thrombosis Research
IS - 3
ER -