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KMID : 0620919990310010042
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Experimental & Molecular Medicine
1999 Volume.31 No. 1 p.42 ~ p.46
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Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways
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S A Saeed/Bukhtiar H Shah
A Siddiqui/K A Qureshi/M Khan/S Rafi/V A Ujan/Y Yaqub/H Rasheed/S A Saeed
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Abstract
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Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 μM) and epinephrine (0.5-2 μM) was inhibited by α2-adrenoceptor blocker (yohimbine; IC50= 0.4 μM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 μM) and nitric oxide (NO) donor, SNAP (IC50=1.6 μM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades.
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KEYWORD
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platelet Aggregation, phospholipase C, calcium channel blockers, epinephrine, 5-hydroxytryptamine,
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