Studies of ethanol actions on recombinant δ-containing γ-aminobutyric acid type A receptors yield contradictory results

被引:51
作者
Borghese, Cecilia M. [1 ]
Harris, R. Adron [1 ]
机构
[1] Univ Texas, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA
关键词
ion channel; inhibitory neurotransmission; delta subunit; allosteric modulation; Xenopus oocyte; electrophysiology;
D O I
10.1016/j.alcohol.2007.03.006
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
The gamma-aminobutyric acid type A receptors (GABA(A)-Rs) display a wide variety of subunit combinations. Drugs such as benzodiazepines have shown differential effects based on GABA(A)-R subunit composition. Actions of alcohols and volatile anesthetics generally do not vary markedly with subunit composition, with low concentrations of ethanol being poor modulators of these receptors. Recent studies showed alpha(-)(4/6) and delta-containing GABA(A)-Rs (located extrasynaptically and responsible for tonic currents in selective brain regions) presenting high sensitivity to low concentrations of ethanol, but these results have not been obtained in other laboratories. We carried out additional experiments varying the receptor level of expression, and GABA and ethanol concentration, but no sensitivity to low concentrations of ethanol was detected. We will discuss these results and attempt an analysis of the possible causes for the discrepancies. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:155 / 162
页数:8
相关论文
共 48 条
[1]   δ-subunit containing GABAA receptor knockout mice are less sensitive to the actions of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol [J].
Boehm, Stephen L., II ;
Homanics, Gregg E. ;
Blednov, Yuri A. ;
Harris, R. Adron .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2006, 541 (03) :158-162
[2]   The δ subunit of γ-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol [J].
Borghese, CM ;
Stórustovu, SI ;
Ebert, B ;
Herd, MB ;
Belelli, D ;
Lambert, JJ ;
Marshall, G ;
Wafford, KA ;
Harris, RA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 316 (03) :1360-1368
[3]   Multiple roles of protein kinases in the modulation of γ-aminobutyric acidA receptor function and cell surface expression [J].
Brandon, NJ ;
Jovanovic, JN ;
Moss, SJ .
PHARMACOLOGY & THERAPEUTICS, 2002, 94 (1-2) :113-122
[4]   Pharmacological characterization of a novel cell line expressing human α4β3δ GABAA receptors [J].
Brown, N ;
Kerby, J ;
Bonnert, TP ;
Whiting, PJ ;
Wafford, KA .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 136 (07) :965-974
[5]   Only high concentrations of ethanol affect GABAA receptors of rat cerebellum granule cells in culture [J].
Casagrande, S. ;
Cupello, A. ;
Pellistri, F. ;
Robello, M. .
NEUROSCIENCE LETTERS, 2007, 414 (03) :273-276
[6]   Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit [J].
Davies, PA ;
Hanna, MC ;
Hales, TG ;
Kirkness, EF .
NATURE, 1997, 385 (6619) :820-823
[7]   Variations on an inhibitory theme:: Phasic and tonic activation of GABAA receptors [J].
Farrant, M ;
Nusser, Z .
NATURE REVIEWS NEUROSCIENCE, 2005, 6 (03) :215-229
[8]   Single channel properties of recombinant GABAA receptors containing γ2 or δ subtypes expressed with α1 and β3 subtypes in mouse L929 cells [J].
Fisher, JL ;
Macdonald, RL .
JOURNAL OF PHYSIOLOGY-LONDON, 1997, 505 (02) :283-297
[9]   GABAA receptor subunit γ2 and δ subtypes confer unique kinetic properties on recombinant GABAA receptor currents in mouse fibroblasts [J].
Haas, KF ;
Macdonald, RL .
JOURNAL OF PHYSIOLOGY-LONDON, 1999, 514 (01) :27-45
[10]   Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to α4/6β3δ GABAA receptors [J].
Hanchar, H. Jacob ;
Chutsrinopkun, Panida ;
Meera, Pratap ;
Supavilai, Porntip ;
Sieghart, Werner ;
Wallner, Martin ;
Olsen, Richard W. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (22) :8546-8551