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Pakistan Journal of Biological Sciences
Year: 2003 | Volume: 6 | Issue: 10 | Page No.: 918 - 924
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Involvement of Cyclooxygenase, Phospholipase C and Map Kinase Pathways in Human Platelet Aggregation Mediated by the Synergistic Interaction of Platelet Activating Factor and Arachidonic Acid
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S.A. Saeed,
H. Rasheed,
S. Kumar,
T.M. Ali,
M.U. Butt,
R.Dhangana,
A. Jafri,
S. Zehra
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A.H. Gilani
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Abstract: This study was conducted to examine the mechanism(s) of synergistic interaction of platelet-activating factor (PAF) and arachidonic acid (AA) in platelet aggregation. We found that the synergism in platelet aggregation mediated by subthershold concentration of PAF (5-40 nM) and AA (0.1-0.2mM) was inhibited by PAF receptor blocker (WEB 2086, IC50= 0.6 µM) showing that the effect is receptor mediated. To examine the role of the downstream signaling pathways, we found that such an interaction was inhibited by calcium channel blockers, diltiazem (IC50= 15 µM) and verapamil (IC50 = 20 µM), as well as by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 6 µM) and MAP kinase inhibitor, PD 98059 (IC50= 3.5 µM). Inhibitor of AA-cyclooxygenase (flurbiprofen: IC50 = 3 µM) also inhibited PAF and AA induced aggregation showing the involvement of COX pathway. On the other hand, herbimycin A, a specific inhibitor of tyrosine light chain kinase (TLCK) and SNAP, a nitric oxide (NO) donor also inhibited PAF and AA-induced aggregation with IC50 values of 15 and 1.7 µM respectively. However, the inhibitor of protein kinase C (chelerythrine; 20 µM)) had no effect on aggregation induced by PAF and AA. These data suggest that the synergism between PAF and AA in platelet aggregation involves activation of PLC, COX, MAP kinase, TLCK and NO signaling pathways. |
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