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Glutamate mediates platelet activation through the AMPA receptor
Glutamate is an excitatory neurotransmitter that binds to the kainate receptor, the N-methyl-D-aspartate (NMDA) receptor, and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). Each receptor was first characterized and cloned in the central nervous system (CNS). Glutam...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275381/ https://www.ncbi.nlm.nih.gov/pubmed/18283118 http://dx.doi.org/10.1084/jem.20071474 |
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author | Morrell, Craig N. Sun, Henry Ikeda, Masahiro Beique, Jean-Claude Swaim, Anne Marie Mason, Emily Martin, Tanika V. Thompson, Laura E. Gozen, Oguz Ampagoomian, David Sprengel, Rolf Rothstein, Jeffrey Faraday, Nauder Huganir, Richard Lowenstein, Charles J. |
author_facet | Morrell, Craig N. Sun, Henry Ikeda, Masahiro Beique, Jean-Claude Swaim, Anne Marie Mason, Emily Martin, Tanika V. Thompson, Laura E. Gozen, Oguz Ampagoomian, David Sprengel, Rolf Rothstein, Jeffrey Faraday, Nauder Huganir, Richard Lowenstein, Charles J. |
author_sort | Morrell, Craig N. |
collection | PubMed |
description | Glutamate is an excitatory neurotransmitter that binds to the kainate receptor, the N-methyl-D-aspartate (NMDA) receptor, and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). Each receptor was first characterized and cloned in the central nervous system (CNS). Glutamate is also present in the periphery, and glutamate receptors have been identified in nonneuronal tissues, including bone, heart, kidney, pancreas, and platelets. Platelets play a central role in normal thrombosis and hemostasis, as well as contributing greatly to diseases such as stroke and myocardial infarction. Despite the presence of glutamate in platelet granules, the role of glutamate during hemostasis is unknown. We now show that activated platelets release glutamate, that platelets express AMPAR subunits, and that glutamate increases agonist-induced platelet activation. Furthermore, we demonstrate that glutamate binding to the AMPAR increases intracellular sodium concentration and depolarizes platelets, which are important steps in platelet activation. In contrast, platelets treated with the AMPAR antagonist CNQX or platelets derived from GluR1 knockout mice are resistant to AMPA effects. Importantly, mice lacking GluR1 have a prolonged time to thrombosis in vivo. Our data identify glutamate as a regulator of platelet activation, and suggest that the AMPA receptor is a novel antithrombotic target. |
format | Text |
id | pubmed-2275381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22753812008-09-17 Glutamate mediates platelet activation through the AMPA receptor Morrell, Craig N. Sun, Henry Ikeda, Masahiro Beique, Jean-Claude Swaim, Anne Marie Mason, Emily Martin, Tanika V. Thompson, Laura E. Gozen, Oguz Ampagoomian, David Sprengel, Rolf Rothstein, Jeffrey Faraday, Nauder Huganir, Richard Lowenstein, Charles J. J Exp Med Articles Glutamate is an excitatory neurotransmitter that binds to the kainate receptor, the N-methyl-D-aspartate (NMDA) receptor, and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). Each receptor was first characterized and cloned in the central nervous system (CNS). Glutamate is also present in the periphery, and glutamate receptors have been identified in nonneuronal tissues, including bone, heart, kidney, pancreas, and platelets. Platelets play a central role in normal thrombosis and hemostasis, as well as contributing greatly to diseases such as stroke and myocardial infarction. Despite the presence of glutamate in platelet granules, the role of glutamate during hemostasis is unknown. We now show that activated platelets release glutamate, that platelets express AMPAR subunits, and that glutamate increases agonist-induced platelet activation. Furthermore, we demonstrate that glutamate binding to the AMPAR increases intracellular sodium concentration and depolarizes platelets, which are important steps in platelet activation. In contrast, platelets treated with the AMPAR antagonist CNQX or platelets derived from GluR1 knockout mice are resistant to AMPA effects. Importantly, mice lacking GluR1 have a prolonged time to thrombosis in vivo. Our data identify glutamate as a regulator of platelet activation, and suggest that the AMPA receptor is a novel antithrombotic target. The Rockefeller University Press 2008-03-17 /pmc/articles/PMC2275381/ /pubmed/18283118 http://dx.doi.org/10.1084/jem.20071474 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Morrell, Craig N. Sun, Henry Ikeda, Masahiro Beique, Jean-Claude Swaim, Anne Marie Mason, Emily Martin, Tanika V. Thompson, Laura E. Gozen, Oguz Ampagoomian, David Sprengel, Rolf Rothstein, Jeffrey Faraday, Nauder Huganir, Richard Lowenstein, Charles J. Glutamate mediates platelet activation through the AMPA receptor |
title | Glutamate mediates platelet activation through the AMPA receptor |
title_full | Glutamate mediates platelet activation through the AMPA receptor |
title_fullStr | Glutamate mediates platelet activation through the AMPA receptor |
title_full_unstemmed | Glutamate mediates platelet activation through the AMPA receptor |
title_short | Glutamate mediates platelet activation through the AMPA receptor |
title_sort | glutamate mediates platelet activation through the ampa receptor |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275381/ https://www.ncbi.nlm.nih.gov/pubmed/18283118 http://dx.doi.org/10.1084/jem.20071474 |
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