Structural determinants of agonist efficacy at the glutamate binding site of N-methyl-D-aspartate receptors

N-methyl-d-aspartate (NMDA) receptors are ligand-gated ion channels assembled from GluN1 and GluN2 subunits. We used a series of N-hydroxypyrazole-5-glycine (NHP5G) partial agonists at the GluN2 glutamate binding site as tools to study activation of GluN1/GluN2A and GluN1/GluN2D NMDA receptor subtyp...

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Bibliographic Details
Published in:Molecular pharmacology 2013-07, Vol.84 (1), p.114-127
Main Authors: Hansen, Kasper B, Tajima, Nami, Risgaard, Rune, Perszyk, Riley E, Jørgensen, Lars, Vance, Katie M, Ogden, Kevin K, Clausen, Rasmus P, Furukawa, Hiro, Traynelis, Stephen F
Format: Article
Language:English
Subjects:
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology
Animals
Binding Sites
Cells, Cultured
Excitatory Amino Acid Agonists - pharmacology
Female
Glutamic Acid - chemistry
Glutamic Acid - metabolism
Glycine - pharmacology
HEK293 Cells
Humans
Protein Structure, Tertiary
Protein Subunits - chemistry
Protein Subunits - metabolism
Receptors, Kainic Acid - metabolism
Receptors, N-Methyl-D-Aspartate - chemistry
Receptors, N-Methyl-D-Aspartate - metabolism
Xenopus laevis - metabolism
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Summary:N-methyl-d-aspartate (NMDA) receptors are ligand-gated ion channels assembled from GluN1 and GluN2 subunits. We used a series of N-hydroxypyrazole-5-glycine (NHP5G) partial agonists at the GluN2 glutamate binding site as tools to study activation of GluN1/GluN2A and GluN1/GluN2D NMDA receptor subtypes. Using two-electrode voltage-clamp electrophysiology, fast-application patch-clamp, and single-channel recordings, we show that propyl- and ethyl-substituted NHP5G agonists have a broad range of agonist efficacies relative to the full agonist glutamate (
ISSN:0026-895X
1521-0111
1521-0111
DOI:10.1124/mol.113.085803