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KMID : 0620920010330040226
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Experimental & Molecular Medicine
2001 Volume.33 No. 4 p.226 ~ p.233
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Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5- hydroxytryptamine
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Sheikh A Saeed/Bukhtiar H Shah
Huma Rasheed/Ibrahim H Rahman/Amir H Shariff/Fatima L Khan/Hina B Rahman/Sara Hanif/Sheikh A Saeed
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Abstract
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Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 μM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.
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KEYWORD
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platelet aggregation, PAF, 5-HT, MAP kinase, synergism,
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