Journal of Pharmacological Sciences (Jan 2007)

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

  • Yong-Ri Jin,
  • Xiang-Hua Han,
  • Jung-Jin Lee,
  • Yong Lim,
  • Tack-Joong Kim,
  • Hwan-Soo Yoo,
  • Jin-Tae Hong,
  • Chong-Kil Lee,
  • Yeo-Pyo Yun

Journal volume & issue
Vol. 105, no. 2
pp. 193 – 200

Abstract

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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