Inhibitory Effects of TA-993 and Its Metabolite MB3 on Platelet Activation Induced by Collagen and U-46619 in Human Platelets

• Published in: Biological & pharmaceutical bulletin 2001, Vol.24(5), pp.501-504
• Main Authors: KATOH, Makoto, KARASAWA, Tadashi, WATANABE, Ayako, TAKAGI, Michino, IKEO, Tomihiro, ODAWARA, Akio
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Adenosine Triphosphate - metabolism; ATP release; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Calcium - metabolism; collagen; Collagen - pharmacology; Diltiazem - analogs & derivatives; Diltiazem - metabolism; Diltiazem - pharmacology; Humans; intracellular calcium; Male; Medical sciences; Pharmacology. Drug treatments; Platelet Activation - drug effects; platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; TA-993; thromboxane; Thromboxane B2 - biosynthesis
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.24.501

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+.