1.Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways.
Bukhtiar H SHAH ; A SIDDIQUI ; K A QURESHI ; M KHAN ; S RAFI ; V A UJAN ; M Y YAKOOB ; H RASHEED ; S A SAEED
Experimental & Molecular Medicine 1999;31(1):42-46
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 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). 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.
Blotting, Western
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Calcium Channel Blockers/pharmacology
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Calcium Signaling*
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Drug Synergism
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Enzyme Activation
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Enzyme Inhibitors/pharmacology
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Epinephrine/pharmacology
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G-Protein, Inhibitory Gi/metabolism*
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GTP-Binding Proteins/metabolism*
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Human
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Phospholipase C/metabolism*
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Phospholipase C/antagonists & inhibitors
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Platelet Aggregation/physiology
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Platelet Aggregation/drug effects*
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Serotonin/pharmacology
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Signal Transduction