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Research ArticleArticle

Acute Effects of Ethanol on Kainate Receptors with Different Subunit Compositions

C. Fernando Valenzuela and Rita A. Cardoso
Journal of Pharmacology and Experimental Therapeutics March 1999, 288 (3) 1199-1206;
C. Fernando Valenzuela
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Rita A. Cardoso
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Abstract

Previous studies showed that recombinant homomeric GluR6 receptors are acutely inhibited by ethanol. This study examined the acute actions of ethanol on recombinant homomeric and heteromeric kainate (KA) receptors with different subunit configurations. Application of 25 to 100 mM ethanol produced inhibition of a similar magnitude of both GluR5-Q and GluR6-R KA receptor-dependent currents in Xenopusoocytes. Ethanol decreased the KA Emaxwithout affecting the EC50 and its effect was independent of the membrane holding potential for both of these receptors subtypes. Ethanol also inhibited homomeric and heteromeric receptors transiently expressed in human embryonic kidney (HEK) 293 cells. In these cells, the expression of heteromeric GluR6-R subunit-containing receptors was confirmed by testing their sensitivity to 1 mM α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. Ethanol inhibited to a similar extent KA-gated currents mediated by receptors composed of either GluR6 or GluR6 + KA1 subunits, and to a slightly lesser extent receptors composed of GluR6 + KA2 subunits. Acute ethanol’s effects were tested on GluR5 KA receptors that are expressed as homomers (GluR5-Q) or heteromers (GluR5-R + KA1 and GluR5-R + KA2). Homomeric and heteromeric GluR5 KA receptors were all inhibited to a similar extent by ethanol; however, there was slightly more inhibition of GluR5-R + KA2 receptors. Thus, recombinant KA receptors with different subunit compositions are all acutely inhibited to a similar extent by ethanol. In light of recent reports that KA receptors regulate neurotransmitter release and mediate synaptic currents, we postulate that these receptors may play a role in acute ethanol intoxication.

Footnotes

  • Send reprint requests to: C. Fernando Valenzuela, M.D., Ph.D., Department of Neurosciences, University of New Mexico, Health Sciences Center, Basic Medical Sciences Building, Room 235 Albuquerque, NM 87131-5223. E-mail: fvalenzuela{at}salud.unm.edu

  • ↵1 This work was supported by National Institutes of Health Grant AA00227 (to C.F.V.)

  • Abbreviations:
    NMDA
    N-methyl-d-aspartate
    AMPA
    α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
    HEK
    human embryonic kidney
    KA
    kainate
    CNS
    central nervous system
    GABAA
    γ-aminobutyric acidA
    • Received September 1, 1998.
    • Accepted October 19, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 3
1 Mar 1999
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Research ArticleArticle

Acute Effects of Ethanol on Kainate Receptors with Different Subunit Compositions

C. Fernando Valenzuela and Rita A. Cardoso
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1199-1206;

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Research ArticleArticle

Acute Effects of Ethanol on Kainate Receptors with Different Subunit Compositions

C. Fernando Valenzuela and Rita A. Cardoso
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1199-1206;
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