Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine
Experimental & Molecular Medicine
; : 226-233, 2001.
Article
em En
| WPRIM
| ID: wpr-144635
Biblioteca responsável:
WPRO
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.
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Texto completo:
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Índice:
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Assunto principal:
Fosforilação
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Pirrolidinonas
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Tromboxano A2
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Técnicas In Vitro
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Cinética
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Diltiazem
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Verapamil
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Fator de Ativação de Plaquetas
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Serotonina
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Ativação Plaquetária
Limite:
Humans
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2001
Tipo de documento:
Article