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DOI: 10.1055/s-0037-1615614
Rho-kinase Is Involved in the Sustained Phosphorylation of Myosin and the Irreversible Platelet Aggregation Induced by PAR1 Activating Peptide
Publikationsverlauf
Received
25. Mai 2000
Accepted after resubmission
12. Oktober 2000
Publikationsdatum:
08. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200103/lookinside/thumbnails/10-1055-s-0037-1615614-1.jpg)
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.
* INSERM, Unité 533, Faculté des Sciences et Techniques de Nantes, Nantes, France
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