Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways.
- Author:
Bukhtiar H SHAH
1
;
A SIDDIQUI
;
K A QURESHI
;
M KHAN
;
S RAFI
;
V A UJAN
;
M Y YAKOOB
;
H RASHEED
;
S A SAEED
Author Information
1. Department of Physiology and Pharmacology, The Aga Khan University, Karachi, Pakistan.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
platelet Aggregation;
phospholipase C;
calcium channel blockers;
epinephrine;
5-hydroxytryptamine
- MeSH:
Blotting, Western;
Calcium Channel Blockers/pharmacology;
Calcium Signaling*;
Drug Synergism;
Enzyme Activation;
Enzyme Inhibitors/pharmacology;
Epinephrine/pharmacology;
G-Protein, Inhibitory Gi/metabolism*;
GTP-Binding Proteins/metabolism*;
Human;
Phospholipase C/metabolism*;
Phospholipase C/antagonists & inhibitors;
Platelet Aggregation/physiology;
Platelet Aggregation/drug effects*;
Serotonin/pharmacology;
Signal Transduction
- From:Experimental & Molecular Medicine
1999;31(1):42-46
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
