Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid

S H Zaman; R Shingai; Robert J Harvey; M G Darlison; E A Barnard

doi:10.1016/0922-4106(92)90106-6

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Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid

Journal article

Peer reviewed

Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid

S H Zaman, R Shingai, Robert J Harvey, M G Darlison and E A Barnard

European Journal of Pharmacology: Molecular Pharmacology, Vol.225(4), pp.321-330

1992

DOI: https://doi.org/10.1016/0922-4106(92)90106-6

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Abstract

cloned subtypes

GABAA receptor

neurosteroid

xenopus oocytes expression

When vertebrate brain poly(A)+ RNA is expressed in Xenopus oocytes the response of the GABA receptors formed is found to be inhibited allosterically by a neurosteroid, pregnenolone sulphate (PS). This negative modulation was reproduced after expressing RNAs enconding bovine GABAA receptor subunits in the combinations α1 + ÃŸ1, or αi + ÃŸ1 + γ2 (where i = 1. 2 or 3). The characteristics of this inhibition vary significantly with the type of the α subunit (α1, α2, or α3) used. When the bovine γ2L alternate form of the γ2 subunit was replaced by the human γ2S subunit, the behaviour was unchanged: the human γ2S subunit used is a newly-cloned form, which encodes a polypeptide with two amino acid differences from the human γ2 subunit previously described. The results of co-application of PS and 3α-hydroxy-5α-pregnan-ol-20-one, a neurosteroid which is a positive modulator of the GABAA receptor, indicate that these act at different sites on the receptor. PS also increases the desensitisation of the receptor by GABA. This effect, also, is α-subunit-type dependent and occurs by an acceleration of the fast phase of desensitisation. © 1992.

Details

Title: Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid
Authors: S H Zaman (Author) - MRC Molecular Neurobiology Unit, United Kingdom
R Shingai (Author) - MRC Molecular Neurobiology Unit, United Kingdom
Robert J Harvey (Author) - MRC Molecular Neurobiology Unit, United Kingdom
M G Darlison (Author) - MRC Molecular Neurobiology Unit, United Kingdom
E A Barnard (Author) - MRC Molecular Neurobiology Unit, United Kingdom
Publication details: European Journal of Pharmacology: Molecular Pharmacology, Vol.225(4), pp.321-330
Publisher: Elsevier BV
Date published: 1992
DOI: 10.1016/0922-4106(92)90106-6
ISSN: 0922-4106
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450335202621
Output Type: Journal article

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