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Journal of Biological Sciences
Year: 2004  |  Volume: 4  |  Issue: 2  |  Page No.: 117 - 121

Calcium Signaling in Human Platelet Aggregation Mediated by Platelet Activating Factor and Calcium Ionophore, A23187

Huma Rasheed, Afshin Hasan Tirmizi, Farah Salahuddin, Nida Batool Rizvi, Mehreen Arshad, Saadia Zohra Farooq and Sheikh Arshad Saeed    

Abstract: The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthershold concentrations of PAF (5-40 nM) and A23187 (0.5- 1 μM) was inhibited by PAF receptor blocker (WEB 2086; IC50=0.65 μM) and calcium channel blockers, verapamil (IC50=18 μM) and diltiazem (IC50=13 μM). While examining the role of the down stream signaling pathways, we found platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50=10 μM), a cyclooxygenase inhibitor (indomethacin; IC50=0.2 μM) and inhibitor of TLCK with IC50 value of 5 μM. The effect was also inhibited by a specific TXA2 receptor antagonist (SQ 29, 548), with very low IC50 value of 0.05 μM. However, The inhibitors of MAP kinase (PD 98059) and, protein kinase C (chelerythrine) had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of PLC/Ca2+, TLCK and COX pathways.

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