Rho-kinase Is Involved in the Sustained Phosphorylation of Myosin and the Irreversible Platelet Aggregation Induced by PAR1 Activating Peptide

K. Missy; M. Plantavid; P. Pacaud; C. Viala; H. Chap; B. Payrastre

doi:10.1055/s-0037-1615614

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 85(03): 514-520
DOI: 10.1055/s-0037-1615614

Review Article

Schattauer GmbH

Rho-kinase Is Involved in the Sustained Phosphorylation of Myosin and the Irreversible Platelet Aggregation Induced by PAR1 Activating Peptide

K. Missy

¹INSERM, Unité 326, Institut Fédératif de Recherche 30, Hôpital Purpan, Toulouse, France

,

M. Plantavid

¹INSERM, Unité 326, Institut Fédératif de Recherche 30, Hôpital Purpan, Toulouse, France

,

P. Pacaud^*

,

C. Viala

¹INSERM, Unité 326, Institut Fédératif de Recherche 30, Hôpital Purpan, Toulouse, France

,

H. Chap

¹INSERM, Unité 326, Institut Fédératif de Recherche 30, Hôpital Purpan, Toulouse, France

,

B. Payrastre

¹INSERM, Unité 326, Institut Fédératif de Recherche 30, Hôpital Purpan, Toulouse, France

› Institutsangaben

Abstract

Summary

We have addressed the role of Rho-kinase in the different steps of thrombin receptor agonist peptide (TRAP) -induced platelet activation. Interestingly, under physiological conditions, incubation of platelets with increasing concentrations of the specific Rho-kinase inhibitor Y-27632 resulted in a dose-dependent reversion of the aggregation induced by 10 μM TRAP, without affecting serotonin secretion. Addition of Y-27632 after three minutes of TRAP stimulation, when the maximal aggregation was reached, resulted in a rapid disaggregation of platelets. Accordingly, the early peak of myosin light chain (MLC) phosphorylation induced by TRAP was not affected by Y-27632 but its sustained phosphorylation, observed during the irreversible phase of aggregation, was dependent of Rho-kinase activity. The rapid decrease in MLC phosphorylation upon Y-27632 treatment correlated well with the specific disappearance of myosin heavy chain from the cytoskeleton and preceded platelet disaggregation. Finally, we provide evidence that secreted ADP, known to play a key role in TRAP-induced irreversible phase of aggregation, was involved in the sustained MLC phosphorylation through Rho-kinase and could be replaced by epinephrine.

Keywords

Rho-kinase - irreversible platelet aggregation - myosin - TRAP

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Referenzen

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