Research article summary (published 14 Sep 1991):

Inverse but not full benzodiazepine agonists modulate recombinant alpha 6 beta 2 gamma 2 GABAA receptors in transfected human embryonic kidney cells.

Full Abstract

We compared the modulation of GABA (gamma-aminobutyric acid)-activated currents by benzodiazepines in recombinant GABAA receptors containing either one of two alpha subunits, alpha 1 or alpha 6. Lüddens et al. (Nature, 346 (1990) 648-651) have previously demonstrated that the alpha 6 subunit is part of a cerebellar receptor subtype which selectively binds Ro15-4513, an antagonist of alcohol-induced motor ataxia. Here we report that the imidazobenzodiazepine Ro15-4513 (ethyl 8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-(1,5-a) (1,4)benzodiazepine-3-carboxylate) reduced GABA-activated currents in recombinant alpha 6 beta 2 gamma 2 and alpha 1 beta 2 gamma 2 receptors, thus acting consistently as an inverse agonist. Moreover, another well characterized negative modulator, DMCM (methyl-4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate), also reduces GABA activated-currents in both receptors. In contrast, flunitrazepam (FNZM), a benzodiazepine agonist, increases GABA-activated currents in alpha 1 beta 2 gamma 2 receptors, but not in alpha 6 beta 2 gamma 2 receptors. This study lends further support to the hypothesis that the binding sites of full and partial inverse agonists are different.

Author information

Author/s: Kleingoor, C (C); Ewert, M (M); von Blankenfeld, G (G); Seeburg, P H (PH); Kettenmann, H (H);

Affiliation: Department of Neurobiology, University of Heidelberg, F.R.G.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neuroscience letters (Neurosci Lett), published in NETHERLANDS. (Language: eng)

Reference: 1991-Sep; vol 130 (issue 2) : pp 169-72

Dates: Created 1992/04/08; Completed 1992/04/08; Revised 2008/11/21;

PMID: 1665550, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Action Potentials - drug effects Azides - pharmacology Benzodiazepines - pharmacology Carbolines - pharmacology Cells, Cultured Ethanol - pharmacology Flunitrazepam - pharmacology

Flunitrazepam - pharmacology Humans Kidney - cytology; embryology Receptors, GABA-A - drug effects; physiology Recombinant Proteins Transfection gamma-Aminobutyric Acid - pharmacology

Associated Chemicals: Azides (0) ; Carbolines (0) ; Receptors, GABA-A (0) ; Recombinant Proteins (0) ; Benzodiazepines (12794-10-4) ; Flunitrazepam (1622-62-4) ; gamma-Aminobutyric Acid (56-12-2) ; Ethanol (64-17-5) ; methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (82499-00-1) ; Ro 15-4513 (91917-65-6)

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