Skip to main content

Research Repository

Advanced Search

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

Zaman, Shahid H.; Shingai, Ryuzo; Harvey, Robert J.; Darlison, Mark G.; Barnard, Eric A.

Authors

Shahid H. Zaman

Ryuzo Shingai

Robert J. Harvey

Mark G. Darlison

Eric A. Barnard



Abstract

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 + ß1, or αi + ß1 + 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.

Citation

Zaman, S. H., Shingai, R., Harvey, R. J., Darlison, M. G., & Barnard, E. A. (1992). Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid. European journal of pharmacology. Molecular pharmacology section, 225(4), 321-330. https://doi.org/10.1016/0922-4106%2892%2990106-6

Journal Article Type Article
Publication Date 1992-04
Deposit Date Jul 27, 2016
Journal European Journal of Pharmacology: Molecular Pharmacology
Print ISSN 0922-4106
Peer Reviewed Peer Reviewed
Volume 225
Issue 4
Pages 321-330
DOI https://doi.org/10.1016/0922-4106%2892%2990106-6
Keywords Neurosteroid, GABAA receptor, Cloned subtypes, Xenopus oocytes expression,
Public URL http://researchrepository.napier.ac.uk/Output/317655
Publisher URL http://www.sciencedirect.com/science/article/pii/0922410692901066






Downloadable Citations