RGD Reference Report - Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. - Rat Genome Database

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Cerebellar GABAA receptor selective for a behavioural alcohol antagonist.

Authors: Luddens, H  Pritchett, DB  Kohler, M  Killisch, I  Keinanen, K  Monyer, H  Sprengel, R  Seeburg, PH 
Citation: Luddens H, etal., Nature 1990 Aug 16;346(6285):648-51.
RGD ID: 61594
Pubmed: (View Article at PubMed) PMID:2166916
DOI: Full-text: DOI:10.1038/346648a0

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.

Annotation

Gene Ontology Annotations    

Cellular Component
membrane  (IDA)

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Gabra1  (gamma-aminobutyric acid type A receptor subunit alpha 1)
Gabra6  (gamma-aminobutyric acid type A receptor subunit alpha6)


Additional Information