Antiplatelet Effect of NQ12: a Possible Mechanism Through the Arachidonic Acid Cascade

• Main Authors: Yong-Ri Jin (Author), Xiang-Hua Han (Author), Jung-Jin Lee (Author), Yong Lim (Author), Tack-Joong Kim (Author), Hwan-Soo Yoo (Author), Jin-Tae Hong (Author), Chong-Kil Lee (Author), Yeo-Pyo Yun (Author)
• Format: Book
• Published: Elsevier, 2007-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

NQ12, an antithrombotic agent, has been reported to display a potent antiplatelet activity. This study was undertaken to reveal the effect of NQ12 on rabbit platelet aggregation and signal transduction involved in the arachidonic acid (AA) cascade. NQ12 concentration-dependently suppressed collagen-, AA-, and U46619-induced rabbit platelet aggregation, with IC50 values of 0.71 ± 0.2, 0.82 ± 0.3, and 0.45 ± 0.1 µM, respectively. In addition, the concentration-response curve of U46619 was shifted to the right after NQ12 treatment, indicating an antagonism on thromboxane (TX) A2 receptors. The collagen-stimulated AA liberation was inhibited by NQ12 in the same pattern as its inhibition of platelet aggregation. Further study revealed that NQ12 potently suppressed AA-mediated TXA2 formation, but had no effect on the PGD2 production, indicating an inhibitory effect on TXA2 synthase, which was supported by a TXA2 synthase activity assay indicating that NQ12 concentration-dependently inhibited TXA2 formation converted from PGH2. On the other hand, the AA-stimulated 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) formation was also suppressed by NQ12. Taken together, these results suggest that NQ12 has a potential to inhibit TXA2 synthase activity and TXA2 receptors, and it can modulate AA liberation as well as 12-HETE formation in platelets. This may be a convincing mechanism for the antithrombotic action of NQ12. Keywords:: antithrombotic agent, platelet aggregation, thromboxane A2

Item Description

1347-8613
10.1254/jphs.FP0071006