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
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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].
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
doi:10.1124/mol.110.064006.
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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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New Insights into the Not-So-New NR3 Subunits of N-Methyl-d-aspartate Receptor: Localization, Structure, and Function
