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

• Jin Yong-Ri

  Research Institute of Veterinary Medicine, CBITRC, Chungbuk National University, Korea

• Han Xiang-Hua

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Lee Jung-Jin

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Lim Yong

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Kim Tack-Joong

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Yoo Hwan-Soo

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Hong Jin-Tae

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Lee Chong-Kil

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

• Yun Yeo-Pyo

  College of Pharmacy, CBITRC, Chungbuk National University, Korea

抄録

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.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 105 (2), 193-200, 2007

  公益社団法人 日本薬理学会

キーワード

• antithrombotic agent
• platelet aggregation
• thromboxane A₂

詳細情報

• CRID: 1390001205179829760
• NII論文ID: 10024316390
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.fp0071006
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 8966019
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8966019
• Web Site: https://search.jamas.or.jp/link/ui/2008098762
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可