Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine..
- Author:
Bukhtiar H SHAH
1
;
Huma RASHEED
;
Ibrahim H RAHMAN
;
Amir H SHARIFF
;
Fatima L KHAN
;
Hina B RAHMAN
;
Sara HANIF
;
Sheikh A SAEED
Author Information
1. Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan.
- Publication Type:Original Article ; In Vitro ; Research Support, Non-U.S. Gov't
- Keywords:
platelet aggregation;
PAF;
5-HT;
MAP kinase;
synergism
- MeSH:
Diltiazem/pharmacology;
Dose-Response Relationship, Drug;
Drug Synergism;
Estrenes/pharmacology;
Flavones/pharmacology;
Human;
In Vitro;
Indomethacin/pharmacology;
Kinetics;
Mitogen-Activated Protein Kinases/metabolism;
Phosphorylation/drug effects;
Platelet Activating Factor/*pharmacology;
Platelet Activation/drug effects;
Platelet Aggregation/*drug effects/physiology;
Pyrrolidinones/pharmacology;
Serotonin/*pharmacology;
Thromboxane A2/biosynthesis;
Verapamil/pharmacology
- From:Experimental & Molecular Medicine
2001;33(4):226-233
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 microM) 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.
