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Circ Res. 2009 Sep 11;105(6):595-603. doi: 10.1161/CIRCRESAHA.109.198861. Epub 2009 Aug 13.

Platelet kainate receptor signaling promotes thrombosis by stimulating cyclooxygenase activation.

Author information

  • 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

RATIONALE:

Glutamate is a major signaling molecule that binds to glutamate receptors including the ionotropic glutamate receptors; kainate (KA) receptor (KAR), the N-methyl-d-aspartate receptor, and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Each is well characterized in the central nervous system, but glutamate has important signaling roles in peripheral tissues as well, including a role in regulating platelet function.

OBJECTIVE:

Our previous work has demonstrated that glutamate is released by platelets in high concentrations within a developing thrombus and increases platelet activation and thrombosis. We now show that platelets express a functional KAR that drives increased agonist induced platelet activation.

METHODS AND RESULTS:

KAR induced increase in platelet activation is in part the result of activation of platelet cyclooxygenase in a mitogen-activated protein kinase-dependent manner. Platelets derived from KAR subunit knockout mice (GluR6(-/-)) are resistant to KA effects and have a prolonged time to thrombosis in vivo. Importantly, we have also identified polymorphisms in KAR subunits that are associated with phenotypic changes in platelet function in a large group of whites and blacks.

CONCLUSIONS:

Our data demonstrate that glutamate regulation of platelet activation is in part cyclooxygenase-dependent and suggest that the KAR is a novel antithrombotic target.

PMID:
19679838
PMCID:
PMC2771168
DOI:
10.1161/CIRCRESAHA.109.198861
[PubMed - indexed for MEDLINE]
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