Altered effects of ethanol in NR2AΔC/ΔC mice expressing C-terminally truncated NR2A subunit of NMDA receptor

Gordey, M.; Mekmanee, L; Módy, István

doi:10.1016/s0306-4522(01)00234-2

Cited by 16 publications

(9 citation statements)

References 48 publications

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“…We found that acute EtOH inhibits NMDAR‐mediated fEPSPs in the CA1 region of neonatal rats; small but significant effects were detected at EtOH concentrations of 40 mM (∼5%) and 80 mM (∼15%). Our findings are in general agreement with those of Gordey and colleagues (2001) who showed that 100 mM EtOH inhibits NMDAR‐mediated fEPSPs by ∼20% in the CA1 region of slices from P4 to 7 C56Bl/6 mice. Other slice electrophysiological studies performed in our laboratory have investigated the modulation of NMDARs by EtOH in pyramidal neurons from another hippocampal subfield; i.e., the CA3 region.…”

Section: Discussionsupporting

confidence: 93%

“…Durand and colleagues (1981) also demonstrated that EtOH (100 mM) had little effect on the amplitude of fEPSPs that were, in part, mediated by AMPARs in the CA1 hippocampal region of adult rats. A 30‐minute application of 100 mM EtOH inhibited non‐NMDAR‐mediated fEPSPs by ∼20% in the CA1 hippocampus of C56Bl/6 mice (Gordey et al., 2001). In addition, EtOH (25 to 75 mM) did not affect the amplitude of AMPAR‐mediated miniature EPSCs in CA1 pyramidal neurons of the rat hippocampus from P12 to 20 rats (Hendricson et al., 2003).…”

Section: Discussionmentioning

confidence: 99%

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Ethanol Acutely Inhibits Ionotropic Glutamate Receptor‐Mediated Responses and Long‐Term Potentiation in the Developing CA1 Hippocampus

Puglia

Valenzuela

2010

Alcoholism Clin & Exp Res

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Ethanol Acutely Inhibits Ionotropic Glutamate Receptor‐Mediated Responses and Long‐Term Potentiation in the Developing CA1 Hippocampus

Puglia

Valenzuela

2010

Alcoholism Clin & Exp Res

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“…The main novel finding of the present study was that the ability of either CGP-37849 or Ro 25-6981 to potentiate ethanol's sedative/hypnotic effects were not significantly altered in NR2A KO mice. In addition, the absence of the NR2A subunit did not significantly alter basal sedative/hypnotic responses to ethanol in the KO mice, consistent with findings in C-terminus NR2A KO mice (Gordey et al, 2001).…”

supporting

confidence: 83%

Functional roles of NMDA receptor NR2A and NR2B subunits in the acute intoxicating effects of ethanol in mice

Boyce-Rustay

Holmes

2005

Synapse

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The present study examined the roles of NR2A and NR2B subunit-containing NMDA receptors in the mediation of the sedative/hypnotic effects of ethanol in mice. The ability of the competitive NMDA antagonist, CGP-37849 (0, 1, or 3 mg/kg), and the NR2B-selective antagonist, Ro 25-6981 (0, 3, or 10 mg/kg), to alter (3 g/kg) ethanol-induced sleep time was measured in C57BL/6J mice and NR2A knockout (KO) mice. The results show that pretreatment with either antagonist significantly potentiated the sedative/hypnotic effects of ethanol in C57BL/6J mice. These effects were not significantly altered in NR2A KO mice. Basal sleep time responses to ethanol were also normal in NR2A KO mice. These findings confirm a major role for NMDA receptors in the acute intoxicating actions of ethanol and provide tentative support for a prepotent role of the NR2B subunit in these effects.

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“…Studies of C-terminally truncated NR2A and NR2B subunits in human embryonic kidney 293 cells demonstrated that a site of action of ethanol is probably at a locus exposed to the extracellular environment (44,45). However, these studies also demonstrated that the C termini of NR2 subunits are important for regulating the ethanol sensitivity of NMDARs.…”

Section: Figmentioning

confidence: 99%

Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-d-aspartate Receptor Function

Alvestad¹,

Grosshans²,

Coultrap³

et al. 2003

Journal of Biological Chemistry

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NMDA1 receptors are ionotropic glutamate receptors that mediate calcium and sodium entry into neurons. In the CA1 region of the hippocampus, activation of these receptors is known to be required for induction of long term potentiation (LTP), a cellular process proposed by many as a possible mechanism of memory formation. Aberrant NMDA receptor function can result in cell death and may have implications in pathophysiologic disorders such as Parkinson's disease and epilepsy as well as age-related dementias like Alzheimer's disease (7-11). NMDA receptors are heteromeric assemblies of NR1 and NR2 subunits. The NR1 family is composed of a single gene, which can be alternatively spliced to generate eight theoretical splice variants (12). The NR2 family includes four genes, each encoding a unique subunit: NR2A, NR2B, NR2C, and NR2D (13). A third gene family, NR3, has been discovered, but the function of these subunits is not well understood. Whereas the NR1 subunit is required for a functional channel, differential incorporation of NR2 subunits regulates receptor function. The NR2 subunits, particularly NR2A and NR2B, have been shown to influence the sensitivity of NMDA receptors to ethanol block in cultured neurons as wells as transfected HEK293 cells and oocytes (14 -17). More recent studies have indicated that NR1 subunits may also play a key role in mediating the effects of ethanol on channel activity (18 -20).Ethanol is known to have widespread effects on the central nervous system. Ethanol inhibits transmission at the NMDAR subtype of glutamatergic excitatory synapses and enhances inhibitory GABAergic synaptic transmission. In addition, we and others have demonstrated that ethanol blocks LTP in the hippocampus (6,(21)(22)(23). Given that NMDA receptors are both required for induction of LTP and inhibited by ethanol, it is likely that inhibition of LTP by ethanol in the hippocampus is due, at least in part, to inhibition of NMDA receptors. The molecular mechanisms of this inhibition however, remain unknown.One hypothesis that we favor is that ethanol may inhibit the NMDAR by reducing its phosphorylation. Indeed, ethanol has been shown to enhance protein-tyrosine phosphatase activity and also inhibit receptor tyrosine kinase activity (24, 25). Moreover, previous studies suggest that Fyn, a member of the Src family of tyrosine kinases, may be a key player in regulating the sensitivity of NMDARs to ethanol in the hippocampus (26 -28

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Altered effects of ethanol in NR2AΔC/ΔC mice expressing C-terminally truncated NR2A subunit of NMDA receptor

Cited by 16 publications

References 48 publications

Ethanol Acutely Inhibits Ionotropic Glutamate Receptor‐Mediated Responses and Long‐Term Potentiation in the Developing CA1 Hippocampus

Ethanol Acutely Inhibits Ionotropic Glutamate Receptor‐Mediated Responses and Long‐Term Potentiation in the Developing CA1 Hippocampus

Functional roles of NMDA receptor NR2A and NR2B subunits in the acute intoxicating effects of ethanol in mice

Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-d-aspartate Receptor Function

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