ArticleThe Journal of biological chemistry2012
Interactions among positions in the third and fourth membrane-associated domains at the intersubunit interface of the N-methyl-D-aspartate receptor forming sites of alcohol action.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Naltrexone and Nalmefene as Modern Psychopharmacotherapy for Alcohol Use Disorder: Modulation of Opioid Receptors and Neurobiological Pathways of Alcohol Action.Biomedicines · 2026Review
- Endothelial NMDA Receptor Involvement in Retinal Neurovascular Damage Following Prenatal Alcohol Exposure in a Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Two gates mediate NMDA receptor activity and are under subunit-specific regulation.Nature communications · 2023Article
- Review
- Effects of ethanol on GluN1/GluN2A and GluN1/GluN2B NMDA receptor-ion channel gating kinetics.Alcoholism, clinical and experimental research · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Analysis of M4 Transmembrane Segments in NMDA Receptor Function: A Negative Allosteric Modulatory Site at the GluN1 M4 is Determining the Efficiency of Neurosteroid Modulation.Frontiers in pharmacology · 2021Article
- From bedside-to-bench: What disease-associated variants are teaching us about the NMDA receptor.The Journal of physiology · 2021Review
- Effects of Ethanol on Synaptic Plasticity and NMDA Currents in the Juvenile Rat Dentate Gyrus.Brain plasticity (Amsterdam, Netherlands) · 2020Article
- Chronic alcohol disrupts hypothalamic responses to stress by modifying CRF and NMDA receptor function.Neuropharmacology · 2020Article
- Positions in the N-methyl-D-aspartate Receptor GluN2C Subunit M3 and M4 Domains Regulate Alcohol Sensitivity and Receptor Kinetics.Alcoholism, clinical and experimental research · 2019Article
- The NMDA receptor intracellular C-terminal domains reciprocally interact with allosteric modulators.Biochemical pharmacology · 2019Article
- GluN2B Subunit of the NMDA Receptor: The Keystone of the Effects of Alcohol During Neurodevelopment.Neurochemical research · 2019Review
- Probing the Structural Dynamics of the NMDA Receptor Activation by Coarse-Grained Modeling.Biophysical journal · 2017Article
- Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors.The Journal of general physiology · 2017Article
- The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System.Cellular and molecular neurobiology · 2017Review
- Two adjacent phenylalanines in the NMDA receptor GluN2A subunit M3 domain interactively regulate alcohol sensitivity and ion channel gating.Neuropharmacology · 2017Article
- Differential effects of TM4 tryptophan mutations on inhibition of N-methyl-d-aspartate receptors by ethanol and toluene.Alcohol (Fayetteville, N.Y.) · 2016Article
- Intersubunit interactions at putative sites of ethanol action in the M3 and M4 domains of the NMDA receptor GluN1 and GluN2B subunits.British journal of pharmacology · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The N-methyl-D-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The predicted structure of the NMDA receptor, based on that of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We tested the hypothesis that these positions interact to regulate receptor kinetics and ethanol sensitivity by using dual substitution mutants. In single-substitution mutants, we found that a position in both subunits adjacent to one previously identified, GluN1(Gly-638) and GluN2A(Phe-636), can strongly regulate ethanol sensitivity. Significant interactions affecting ethanol inhibition and receptor deactivation were observed at four pairs of positions in GluN1/GluN2A: Gly-638/Met-823, Phe-639/Leu-824, Met-818/Phe-636, and Leu-819/Phe-637; the latter pair also interacted with respect to desensitization. Two interactions involved a position in M4 of both subunits, GluN1(Met-818) and GluN2A(Leu-824), that does not by itself alter ethanol sensitivity, whereas a previously identified ethanol-sensitive position, GluN2A(Ala-825), did not unequivocally interact with any other position tested. These results also indicate a shift by one position of the predicted alignment of the GluN1 M4 domain. These findings have allowed for the refinement of the NMDA receptor M domain structure, demonstrate that this region can influence apparent agonist affinity, and support the existence of four sites of alcohol action on the NMDA receptor, each consisting of five amino acids at the M3-M4 domain intersubunit interfaces.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.