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Molecular Pharmacology

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Review ArticleMINIREVIEWS

New Insights into the Not-So-New NR3 Subunits of N-Methyl-d-aspartate Receptor: Localization, Structure, and Function

Chian-Ming Low and Karen Siaw-Ling Wee
Molecular Pharmacology July 2010, 78 (1) 1-11; DOI: https://doi.org/10.1124/mol.110.064006
Chian-Ming Low
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Karen Siaw-Ling Wee
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Abstract

The NR3 subunits (NR3A and NR3B) are new players in a well established field of N-methyl-d-aspartate (NMDA) receptors, previously involving the NR1 and NR2 subunits. Their incorporation into conventional NMDA receptors forms glutamate-activated NR1/NR2/NR3 triheteromers, whereas the omission of the glutamate-binding NR2 subunits results in excitatory glycine-activated NR1/NR3 diheteromers. These NR3-containing NMDA receptors exhibit several differences in receptor properties compared with the conventional NR1/NR2 receptors. This review highlights the major landmarks that have been achieved in the past decade or so involving NR3 subunit research in four key areas: the spatiotemporal mapping of NR3 protein, the structural elucidation of NR3 domains, pharmacological characterization of NR3-containing receptors, and the successful generation of NR3 knockout/transgenic animals. It is expected that further characterization of their functional roles coupled with the identification of endogenous and exogenous ligands will eventually advance the understanding of the basic pharmacology and the complex role of NMDA receptors in higher brain functions and neurological disorders.

Footnotes

  • This work was supported by the ARF(NUS) [Grant 184-000-160-112]; the National Medical Research Council [Grant 1024/2005]; and the Biomedical Research Council [Grants 05/1/21/19/376, 09/1/21/19/617].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.064006.

  • ABBREVIATIONS:

    NMDA
    N-methyl-d-aspartate
    AMPA
    α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid
    iGlu
    ionotropic glutamate
    ATD
    amino-terminal domain
    CTD
    cytoplasmic terminal domain
    S1S2
    ligand binding domain
    PSD
    postsynaptic density
    HEK
    human embryonic kidney
    DCS
    d-cycloserine
    ACPC
    1-aminocyclopropane-1-carboxylic acid
    ACBC
    1-aminocyclobutane-1-carboxylic acid
    5,7-DCKA
    5,7-dichlorokynurenic acid
    bp
    base pair(s)
    Tg
    transgenic
    LTP
    long-term potentiation
    AP5
    2-amino-5-phosphonopentanoic acid
    L-689560
    trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline
    MK-801
    5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)
    L701324
    7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolinone
    L689560
    trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline
    CGP78608
    [(1S)-1-[[(7-bromo-1,2,3,4-tetrahydro-2,3-dioxo-5-quino xalinyl)methyl]amino]ethyl]phosphonic acid
    MDL-29951
    3-(4,6-dichloro-2-carboxyindol-3-yl)propionic acid
    ALX-1393
    O-[(2-benzyloxyphenyl-3-flurophenyl)methyl]-L-serine.

  • Received February 8, 2010.
  • Accepted March 24, 2010.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 78 (1)
Molecular Pharmacology
Vol. 78, Issue 1
1 Jul 2010
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Review ArticleMINIREVIEWS

New Insights into the Not-So-New NR3 Subunits of N-Methyl-d-aspartate Receptor: Localization, Structure, and Function

Chian-Ming Low and Karen Siaw-Ling Wee
Molecular Pharmacology July 1, 2010, 78 (1) 1-11; DOI: https://doi.org/10.1124/mol.110.064006

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Review ArticleMINIREVIEWS

New Insights into the Not-So-New NR3 Subunits of N-Methyl-d-aspartate Receptor: Localization, Structure, and Function

Chian-Ming Low and Karen Siaw-Ling Wee
Molecular Pharmacology July 1, 2010, 78 (1) 1-11; DOI: https://doi.org/10.1124/mol.110.064006
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