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Two Adjacent Phenylalanines In The Nmda Receptor Glun2a Subunit M3 Domain Interactively Regulate Alcohol Sensitivity And Ion Channel Gating, Hong Ren, Yulin Zhao, Man Wu, Donard S. Dwyer, Robert W. Peoples
Two Adjacent Phenylalanines In The Nmda Receptor Glun2a Subunit M3 Domain Interactively Regulate Alcohol Sensitivity And Ion Channel Gating, Hong Ren, Yulin Zhao, Man Wu, Donard S. Dwyer, Robert W. Peoples
Biological Sciences Faculty Research and Publications
The N-methyl-d-aspartate (NMDA) receptor is a key target of ethanol action in the central nervous system. Alcohol inhibition of NMDA receptor function involves small clusters of residues in the third and fourth membrane-associated (M) domains. Previous results from this laboratory have shown that two adjacent positions in the M3 domain, F636 and F637, can powerfully regulate alcohol sensitivity and ion channel gating. In this study, we report that these positions interact with one another in the regulation of both NMDA receptor gating and alcohol action. Using dual mutant cycle analysis, we detected interactions among various substitution mutants at these …
A Cytotoxic, Co-Operative Interaction Between Energy Deprivation And Glutamate Release From System XC− Mediates Aglycemic Neuronal Cell Death, Trista L. Thorn, Yan He, Nicole A. Jackman, Doug Lobner, James A. Hewett, Sandra J. Hewett
A Cytotoxic, Co-Operative Interaction Between Energy Deprivation And Glutamate Release From System XC− Mediates Aglycemic Neuronal Cell Death, Trista L. Thorn, Yan He, Nicole A. Jackman, Doug Lobner, James A. Hewett, Sandra J. Hewett
Biological Sciences Faculty Research and Publications
The astrocyte cystine/glutamate antiporter (system xc−) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc− expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone or with neurons—to remove glutamate from the extracellular space. Instead, we …
Different Sites Of Alcohol Action In The Nmda Receptor Glun2a And Glun2b Subunits, Yulin Zhao, Hong Ren, Donard S. Dwyer, Robert W. Peoples
Different Sites Of Alcohol Action In The Nmda Receptor Glun2a And Glun2b Subunits, Yulin Zhao, Hong Ren, Donard S. Dwyer, Robert W. Peoples
Biological Sciences Faculty Research and Publications
The NMDA receptor is a major target of alcohol action in the CNS, and recent behavioral and cellular studies have pointed to the importance of the GluN2B subunit in alcohol action. We and others have previously characterized four amino acid positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN2A subunit that influence both ion channel gating and alcohol sensitivity. In this study, we found that substitution mutations at two of the four corresponding positions in the GluN2B subunit, F637 and G826, influence ethanol sensitivity and ion channel gating. Because position 826 contains a glycine residue …
Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker
Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker
Biomedical Sciences Faculty Research and Publications
Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system xc−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xc−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xc−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the …