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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...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
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.
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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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