Inhibitory effects of TA-993 and its metabolite MB3 on platelet activation induced by collagen and U-46619 in human platelets.
In the present study, we investigated the effects of TA-993 and its metabolite MB3 on platelet activation in vitro. TA-993 and MB3 concentration-dependently inhibited platelet aggregation and ATP release induced by collagen in human platelets. Thromboxane (Tx) A2 formation, as determined by the production of TxB2, and the increase in intracellular Ca2+ concentration ([Ca2+]i) were also suppressed by TA-993 and MB3. TA-993 and MB3 did not inhibit TxA2 formation caused by arachidonic acid. These results suggest that the inhibition of platelet activation by TA-993 and MB3 is partly mediated by an inhibition of TxA2 formation at a step prior to cyclooxygenase. Furthermore, TA-993 and MB3 inhibited U-46619-induced platelet aggregation without blockade of the increase in [Ca2+]i, suggesting that they are likely to exert some additional effects on the intracellular events induced by Ca2+.
Katoh
M
M
Discovery Research Laboratory, Tanabe Seiyaku, Co., Ltd., Toda Saitama, Japan. katoh-m@tanabe.co.jp
Karasawa
T
T
Watanabe
A
A
Takagi
M
M
Ikeo
T
T
Odawara
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D004110:Diltiazem / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D010975:Platelet Aggregation Inhibitors; C097363:TA 993; D013929:Thromboxane B2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D003094:Collagen; D004110:Diltiazem; D002118:Calcium