Expression and pharmacology of human GABAA receptors containing γ3 subunits

doi:10.1016/0922-4106(95)90070-5

European Journal of Pharmacology: Molecular Pharmacology

Volume 291, Issue 3, 30 November 1995, Pages 301-309

https://doi.org/10.1016/0922-4106(95)90070-5 Get rights and content

Abstract

A cDNA encoding the γ3 subunit of the human GABA_A receptor has been obtained by molecular cloning. Its deduced amino acid sequence shows a high level of sequence identity with the published mouse and rat sequences (96%). The ligand binding pharmacology of the benzodiazepine site formed by stably-expressed human α5β3γ2S GABA_A receptor subtypes have been compared for a number of ligands. Benzodiazepine site ligands were found to be either non-selective or γ2-selective, with the exception of CL218,872, which was found to be 10-fold selective for the α5β3γ3-containing subtype. Two benzodiazepine site ligands, Rol15-4513 and FG8205 were more efficacious at α5β3β3 receptors than αβ3γ2 receptors expressed in Xenopus oocytes. CL218,872, which is partial agonist at α1 containing receptors, had no intrinsic activity at either α5β3γ2 or α5β3γ3. α1β2γ2S and α1β2γ3 human GABA_A receptors were also expressed in Xenopus oocytes and their benzodiazepine pharmacology investigated. Both in the EC₅₀ and efficacy of benzodiazepine site ligands were influence by the type of γ subunit coexpressed with α1 β2.

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Expression and pharmacology of human GABAA receptors containing γ3 subunits

Abstract

Brain Res.

J. Biol. Chem.

FEBS Lett.

Neuron

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the β3 subunit of the Type A γ-aminobutyric acid receptor

Phenotypic consequences on deletion of the β3, α5, γ3 subunit of the type A γ-aminobutyric acid receptor in mice

Multiple benzodiazepine receptors: no reason for anxiety

Trends Pharmacol. Sci.

Molecular pharmacology of γ-aminobutypric acid type A agonists and partial agonists in oocytes injected with different α, β, and γ receptor subunit combinations

Mol. Pharmacol.

Five subtypes of type A γ-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies

The γ-aminobutyric acid receptor γ3 subunit gene (GABRG3) is tightly linked to the α5 subunit gene (GABRA5) on human chromosome15q11-q13 and is transcribed in the same orientation

Genomics

Stable expression on mammalian type A γ -aminobutyric acid receptors in mouse cells: Demonstration of functional assembly of benzodiazepine-responsive sites

Cloning of cDNA sequences encoding human α2 and α3 γ-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant α1-, α2, α3-, and α5-containing human γ-aminobutyric acidA receptors

Mol. Pharmacol.

Role of the β subunit in determining the pharmacology of human γ-aminobutyric acid type A receptors

Mol. Pharmacol.

The third γ subunit of the γ-aminobutyric acid type A receptor family

FISH ordering of reference markers and of the gene for the α5 subunit of the γ-aminobutyric acid receptor (GABRA5) within the Angelman and PraderWilli syndrome chromosomal regions

Hum. Mol. Genet.

Expression and pharmacology of human GABA_A receptors containing γ3 subunits

Cloning of cDNA sequences encoding human α2 and α3 γ-aminobutyric acid_A receptor subunits and characterization of the benzodiazepine pharmacology of recombinant α1-, α2, α3-, and α5-containing human γ-aminobutyric acid_A receptors