The gamma 3-subunit of the GABAA-receptor confers sensitivity to benzodiazepine receptor ligands.

Détails

ID Serval
serval:BIB_C5175B43744F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The gamma 3-subunit of the GABAA-receptor confers sensitivity to benzodiazepine receptor ligands.
Périodique
FEBS Letters
Auteur⸱e⸱s
Knoflach F., Rhyner T., Villa M., Kellenberger S., Drescher U., Malherbe P., Sigel E., Möhler H.
ISSN
0014-5793[print], 0014-5793[linking]
Statut éditorial
Publié
Date de publication
1991
Volume
293
Numéro
1-2
Pages
191-194
Langue
anglais
Résumé
The gamma 3-subunit of the GABAA-receptor in rat brain has been identified by molecular cloning. When co-expressed with the alpha 5- and beta 2-subunits in transfected cells a high potency for GABA (Ka = 4.9 +/- 1.2 microM) and a strong cooperativity in gating the channel (H = 1.9 +/- 0.2) was observed. The GABA response was potentiated in the presence of flunitrazepam and reduced by beta CCM. An analogous bi-directional modulation of the GABA response was observed with diazepam and DMCM as tested with the subunit combinations alpha 1 beta 2 gamma 3 and alpha 3 beta 2 gamma 3 expressed in Xenopus oocytes. Since the benzodiazepine receptor ligands were virtually inactive in the absence of the gamma 3-subunit, as tested with the alpha 3 beta 2- and alpha 5 beta 2-subunit combinations, the gamma 3-subunit is a prerequisite for the benzodiazepine receptor sensitivity of the expressed GABAA-receptors. The gamma 3-subunit could functionally replace the gamma 2-subunit with regard to the bi-directional allosteric drug modulation.
Mots-clé
Amino Acid Sequence, Animals, Base Sequence, Benzodiazepines/metabolism, Benzodiazepines/pharmacology, Brain/metabolism, Cloning, Molecular, Diazepam/pharmacology, Dose-Response Relationship, Drug, Flunitrazepam/pharmacology, Molecular Sequence Data, Rats, Receptors, GABA-A/drug effects, Receptors, GABA-A/genetics, gamma-Aminobutyric Acid/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 12:45
Dernière modification de la notice
20/08/2019 15:40
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