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  Cerebellar GABAA receptor selective for a behavioural alcohol antagonist

Lüddens, H., Pritchett, D. B., Köhler, M., Killisch, I., Keinänen, K., Monyer, H., et al. (1990). Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature, 346, 648-651. doi:10.1038/346648a0.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-7384-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-7385-8
Genre: Journal Article

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Lüddens, Hartmut, Author
Pritchett, Dolan B., Author
Köhler, Martin1, Author              
Killisch, Iris1, Author              
Keinänen, Kari, Author
Monyer, Hannah1, Author              
Sprengel, Rolf1, 2, 3, Author              
Seeburg, Peter H.1, Author              
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Rolf Sprengel Group, Max Planck Institute for Medical Research, Max Planck Society, ou_1497741              
3Olfaction Web, Max Planck Institute for Medical Research, Max Planck Society, ou_1497733              

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 Abstract: Benzodiazepines are widely prescribed anxiolytics and anticonvulsants which bind with high affinity to sites on the GABAA receptor/Cl- channel complex and potentiate the effect of the neurotransmitter GABA (gamma-aminobutyric acid). The heterogeneity of benzodiazepine recognition sites in the central nervous system was revealed by studies showing different classes of GABAA receptor subunits (classes alpha, beta and gamma) and variant subunits in these classes, particularly in the alpha-class. Expression of recombinant subunits produces functional receptors; when certain alpha-variants are coexpressed with beta- and gamma-subunits the resulting receptors have pharmacological properties characteristic of GABAA-benzodiazepine type I or type II receptors. The alpha-variants are differentially expressed in the central nervous system and can be photoaffinity-labelled with benzodiazepines. Here we report a novel alpha-subunit (alpha 6) of cerebellar granule cells. We show that recombinant receptors composed of alpha 6, beta 2 and gamma 2 subunits bind with high affinity to the GABA agonist [3H]muscimol and the benzodiazepine [3H]Ro15-4513 but not the other benzodiazepines or beta-carboniles. The same distinctive pharmacology is observed with GABAA receptors from rat cerebellum immunoprecipitated by an antiserum specific for the alpha 6 subunit. We conclude that this alpha-subunit is part of a cerebellar receptor subtype, selective for Ro15-4513, an antagonist of alcohol-induced motor incoordination and ataxia.

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Language(s): eng - English
 Dates: 1990-04-091990-05-241990-08-16
 Publication Status: Published in print
 Pages: 4
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 Rev. Type: Peer
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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 346 Sequence Number: - Start / End Page: 648 - 651 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238