The antiplatelet activity of tetramethylpyrazine is mediated through activation of NO synthase.
Tetramethylpyrazine (TMPZ) is an active ingredient of a Chinese herbal medicine (Ligusticum wallichii Franchat). In this study, TMPZ (50-200 microM) significantly increased production of nitrate and cyclic GMP in human platelets within a 15-min incubation period. TMPZ concentration-dependently inhibited intracellular Ca2+ mobilization in human platelets stimulated by collagen (5 microg/ml). Furthermore, TMPZ concentration (50 and 200 microM)- and time (15 and 30 min)-dependently triggered endothelial-type constitutive nitric oxide synthase (ecNOS) protein expression in human platelets. These results indicated that TMPZ at micromolar concentrations stimulated nitric oxide production in human platelets via a novel mechanism that activated ecNOS protein expression.
Sheu
J R
JR
Graduate Institute of Medical Sciences & Department of Pharmacology, Taipei Medical College, Taiwan. sheujr@tmc.edu.tw
Kan
Y C
YC
Hung
W C
WC
Lin
C H
CH
Yen
M H
MH
D001792:Blood Platelets / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood; D004789:Enzyme Activation; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D002118:Calcium; C017953:tetramethylpyrazine