Antiplatelet Actions of 2-Bromo-3-(.3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthaleneflione (TPN2)

2-Bromo-3-(3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthalenedione (TPN2)의 항혈소판 작용

  • 최소연 (아주대학교 의과대학 생리학교실) ;
  • 김민화 (아주대학교 의과대학 생리학교실) ;
  • 이수환 (아주대학교 의과대학 생리학교실) ;
  • 정이숙 (아주대학교 의과대학 생리학교실) ;
  • 백은주 (아주대학교 의과대학 생리학교실) ;
  • 유충규 (이화여자대학교 약학대학) ;
  • 문창현 (아주대학교 의과대학 생리학교실)
  • Published : 1999.09.01

Abstract

The effects of 2-bromo-3-(3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthalenedione(TPN2), a synthetic vitamin K derivative, on platelet aggregation and its action mechanisms were investigated in rat platelet. TPN2 inhibited the platelet aggregation induced by collagen($10\mu\textrm{g}$/ml), thrombin(0.1 U/ml), A23187($10\mu\textrm{M}$) and arachidonic acid($100\mu\textrm{M}$) in concentration-dependent manner with $IC_{50}$ values of 6.5$\pm$1.3, 59.3$\pm$4.5, 13.0$\pm$2.37 and 2.9$\pm$$1.0\mu\textrm{M}$, respectively. Collagen-induced serotonin release was significantly reduced by TPN2. The elevation of intracellular free $Ca^{2+}$ concentration ([$Ca^{2+}$]i) by collagen stimulation was greatly decreased by the pretreatment of TPN2, which was due to the inhibition of calcium release from intracellular store and influx from outside of the cell. TPN2 also significantly reduced the thromboxane $A_2$($TXA_2$) formation in a concentration-dependent manner. The collagen-induced arachidonic acid (AA) release in [$^3H$]-AA incorporated platelet, an indicative of the phospholipase $A_2$ activity, was decreased by TPN2 pretreatment. TPN2 significantly inhibited the activity of thromboxane synthase, but did not affect the cyclooxygenase activity. From these results. it is suggested that TPN2 exert its antiplatelet activity through the inhibition of the intra-cellular $Ca^{2+}$ mobilization and the decrease of the $TXA_2$ synthesis.

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