Pakistan Journal of Biological Sciences1028-88801812-5735Asian Network for Scientific Information10.3923/pjbs.2003.918.924SaeedS. A.RasheedH. KumarS. AliT. M.ButtM. U.DhanganaR. JafriA. ZehraS. GilaniA. H.102003610This 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.]]>Anderson, B.O., D.D. Bensard and A.H. Harken,1991172415424Animesh, D., K.P. Anjan and D.S. Shivendra,199037519525Benveniste, J., P.M. Henson and C.G. Cochrane,197213613561377Borsch-Haubold, A.G., S. Pasquet and S.P. Watson,19982732876628772Brass, L.F., J.A. Hoxie and D.R. Manning,199370217223Chesney, C.M., D.D. Pifer, L.W. Byers and E.E. Muirhead,198259582585Crabos, M., D. Fabbro, S. Stabel and P. Erne,1992288891896DeFily, D.V., L. Kuo and W.M. Chilian,199627020942099Della Rocca, G.J., S. Mausley, Y. Daaka, R.J. Lefkowitz and L.M. Luttrell,19992741397813984DellaRocca, G.J., T.V. Biesen, Y. Daaka, K.D. Luttrell, L.M. Luttrell and R.J. Lefkowitz,19972721912519132Dutilh, C.C., E. Haddeman, G.H. Jouvenaz, F. Ten Hoor and D.H. Nugteren,197914241246Ferrel, J.E. and G.S. Martin,1988836033610Gimeno, M.F., M.A. Shattner, E. Borda, A.L. Gimeno and M.A. Lazzari,198311109119Golden, A. and H. Yamamura,198986901905Heemskerk, J.W.M. and O. Sage,19945 295316Hirafuji, M. and H. Shinoda,1991in vitro.]]>13613561377McNicol, A., C.L. Philpott, T.S. Shibou and S.J. Israels,19985517591767Montrucchio, G., C. Alloatti and G. Camussi,20008016691699Obberghen-Schilling, E.V. and J. Pouyssegur,199370163167Offermanns, S., C.F. Toombs, Y.H. Hu and M.I. Simon,1997389183186Ohkubu, S., N. Nakahata and Y. Ohizumi,19962+ pathway in rabbit platelets.]]>11710951104Okuma, M., T. Hirata, F. Ushikubi, A. Kakizuka and S. Narumiya,1996487782Ostermann, G., U. Till and K. Thielmann,19841984Saeed, S.A., B.H. Shah, N. Khan and A.H. Gilani,199725219221Shah, B.H. and S.A. Saeed,199589157164Shah, B.H., A. Siddiqui, K.A. Qureshi, M. Khan and S. Rafi et al.,19992+ signalling.]]>314246Shah, B.H., B. Safdar, S.S. Virani, Z. Nawaz, S.A. Saeed and A.H. Gilani,1997Acacia nilotica is due to blockade of calcium influx through membrane calcium channels.]]>29251255Shah, B.H., I. Lashari, S. Rana, O. Saeed, H. Rasheed and S.A. Saeed,200042479483Siess, W.,19896958178Somova, L.,19962-thromboxane A2 pathway in platelet aggregation and activity of Dahl salt-sensitive rat- a sulotroban study.]]>18309313Tazawa, R., E.D. Green, K. Ohashi, K.K. Wu and L.H. Wang,1996334349356Wang, L.L., Q.B. Mei, D.H. Zhao and Z.A. Guo,2000in vitro.]]>21623626Ware, J.A., M. Smith and E.W. Salzman,198780267271