Antiplatelet Activity of 2-(4-Cyanophenyl)amino-1,4-naphthalenedione-3-pyridinium perchlorate (PQ5)

Abstract

The effect of 2-(4-cyanophenyl)amino-1,4-naphthalenedione-3-pyridinium perchlorate (PQ5) on pla-telet aggregation and its action mechanisms were investigated with rat platelet. PQ5 inhibited the platelet aggregation induced by collagen (6 pg/ml), thrombin (0.4 U/ml) and A23187 (3 p.M) in concentration-dependent manner with IC50 values of 5.50, 25.89 and 37.12 p.M, respectively. PQ5 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 indication of the phospholipase A2 activity, was decreased by PQ5 pretreatment PQ5 significantly inhibited the activity of thromboxane synthase only at high concentration (100 μM), but did not affect the cyclooxygenase activity at all. Collagen-induced ATP release was significantly reduced by PQ5. Calcium-induced platelet aggregation experiment suggests that the elevation of intracellular free Cat+ concentration ([Ca2+];) by collagen stimulation is decreased by the pretreatment of PQ5, which is due to the inhibition of calcium release from intracellular store and influx from outside of the cell. PQ5 did not showed the effect of anticoagulation as prothrombin time (PT) or activated partial thromboplastin time (APTT). From these results, it is suggested that PQ5 exerts its antiplatelet activity through the inhibition of the intracellular Cali mobilization and the decrease of the TXA2 synthesis.