Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents



ID: 420232.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
Glutamate mediates platelet activation through the AMPA receptor
Translation of Title:Glutamate mediates platelet activation through the AMPA receptor
Authors:Morrell, C. N.; Sun, H.; Ikeda, M.; Beique, J. C.; Swaim, A. M.; Mason, E.; Martin, T. V.; Thompson, L. E.; Gozen, O.; Ampagoomian, D.; Sprengel, Rolf; Rothstein, J.; Faraday, N.; Huganir, R.; Lowenstein, C. J.
Language:English
Date of Publication (YYYY-MM-DD):2008-02-18
Title of Journal:J Exp Med
Journal Abbrev.:J Exp Med
Volume:205
Issue / Number:3
Start Page:575
End Page:584
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Glutamate is an excitatory neurotransmitter that binds to the kainate receptor, the N−methyl−D−aspartate (NMDA) receptor, and the {alpha}−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.
Last Change of the Resource (YYYY-MM-DD):--
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI f�r medizinische Forschung/Abteilung Molekulare Neurobiologie
Identifiers:LOCALID:7171
URI:http%3A%2F%2Fjem.rupress.org%2Fcgi%2Freprint%2F205...
URI:http%3A%2F%2Fjem.rupress.org%2Fcgi%2Fcontent%2Fful...
URI:http%3A%2F%2Fjem.rupress.org%2Fcgi%2Fcontent%2Fabs...
DOI:10.1084%2Fjem.20071474
Full Text:
Sorry, no privileges
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.