Research Article
Mechanism of Inhibitory Action of Cyclooxygenase-2 Inhibitors in Human Platelets

S.A. Saeed, H. Rasheed, T.M. Ali, Y. Qazi, S. Kabraji, L. Paul, R. Khan, F.A. Hussain and S. Ahmad

Journal of Biological Sciences, 2004, 4(4), 515-520.

Abstract

This study was conducted to investigate the effects of nimesulide in platelet aggregation. It shows that nimesulide (1-100 μ M) inhibited platelets aggregation induced by adrenaline, (20-200 μ M). It also inhibed thromboxane A2 (TXA2) formation by platelets at low concentration (IC50; 1 μ M). However, much lower concentrations of nimesulide (0.01-0.1 μ M) potentiated the aggregatory response of subthreshold concentrations of adrenaline (0.2-2 μ M). Such an effect was blocked by Ca2+-channel blockers, verapamil and diltiazem (IC50: 7 and 46 μ M, respectively), nitric oxide donor, SNAP (IC50: 2 μ M) and cinchonine (10 nM) but not by genistein (up to 10 μ M). These results are indicative of the concentration-dependent dual effects of nimesulide on human platelet aggregation. The synergistic effect of low doses of nimesulide and adrenaline seems to be mediated through inhibition of multiple signaling pathways.

ASCI-ID: 38-922

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