PMID: 8584509Aug 1, 1995Paper

Effects of ethanol on recombinant rat GABAA receptors: [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding study

Pharmacology & Toxicology
E R KorpiH Lüddens

Abstract

To determine the roles of the alternatively spliced short and long forms of the gamma 2 subunit in the effect of ethanol on the GABAA receptor function, picrotoxin-sensitive [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding was studied in recombinant rat alpha 1 beta 2 gamma 2 and alpha 6 beta 2 gamma 2 receptors expressed in human embryonic kidney 293 cells. Ethanol (10-500 mM) in the absence of added GABA had only minor effects on [35S]TBPS binding irrespective of the gamma 2 splice variant, its effects being greater in alpha 6 beta 2 gamma 2 than in alpha 1 beta 2 gamma 2 receptors. Ethanol (100 mM) decreased the binding in all four subunit combinations at various concentrations of GABA, again an effect independent of the gamma 2 variant. The two gamma 2 variants had different effects on GABA modulation of the binding, with the long gamma 2 variant decreasing the efficiency of GABA inhibition in alpha 6 beta 2 gamma 2 receptors and enhancing the biphasic GABA stimulation and inhibition in alpha 1 beta 2 gamma 2 receptors. The findings confirm the importance of the alpha subunits in the allosteric interactions between the convulsant binding site and other effector sites, which can be modified only to a minor extent by ...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jun 1, 1992·Current Opinion in Neurobiology·W Wisden, P H Seeburg
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P WhitingL L Iversen
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Jun 14, 1993·FEBS Letters·E SigelP Malherbe

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Citations

Jul 20, 2002·Progress in Neurobiology·Esa R KorpiHartmut Lüddens

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