The antiplatelet activity of PMC, a potent α-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase

Joen R. Sheu, Cheng R. Lee, Chang C. Lin, Ya C. Kan, Chien-Huang Lin, Wei C. Hung, Yen M. Lee, Mao H. Yen

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

1. PMC, a potent α-tocopherol derivative, dose-dependently (5-25 μM) inhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). 2. PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. 3. PMC (10 and 25 μM) significantly inhibited collagen-stimulated thromboxane A2 (TxA2) formation in human platelets. On the other hand, PMC (25 and 100 μM) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 μM) did not affect the thromboxane synthetase activity of aspirin-treated platelet microsomes. 4. PMC (10 and 25 μM) markedly inhibited the exogenous arachidonic acid (100 μM)-induced prostaglandin E2 (PGE2) formation in the presence of imidazole (600 μM) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. 5. We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclo-oxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA2 formation, and finally inhibition of [Ca2+](i) mobilization and ATP-release.

Original languageEnglish
Pages (from-to)1206-1212
Number of pages7
JournalBritish Journal of Pharmacology
Volume127
Issue number5
DOIs
Publication statusPublished - 1999

Keywords

  • α-tocopherol
  • Cyclo-oxygenase
  • Platelet aggregation
  • PMC

ASJC Scopus subject areas

  • Pharmacology

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