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

다국어 초록 (Multilingual 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 ㎍/ml), thrombin(0.1 U/ml), A23187(10 μM) and arachidonic acid(100 μM) in concentration-dependent manner with IC_(50) values of 6.5 ±1.3, 59.3 ± 4.5, 13.0 ± 2.37 and 2.9 ±1.0 μM, 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 A₂(TXA₂) formation in a concentration-dependent manner. The collagen-induced arachidonic acid (AA) release in [3H]-AA incorporated platelet, an indicative of the phospholipase A₂ 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 intracellular Ca^(2+) mobilization and the decrease of the TXA₂ synthesis.