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PMID: 2170110 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors.

The EMBO journal ·Vol. 9 ·No. 10 ·1990-10-00 ·Pages 3261-7

Ymer S, Draguhn A, Wisden W, Werner P, Keinänen K, Schofield PR, Sprengel R, Pritchett DB, Seeburg PH

Abstract

The GABAA receptor gamma 1 subunit of human, rat and bovine origin was molecularly cloned and compared with the gamma 2 subunit in structure and function. Both gamma subunit variants share 74% sequence similarity and are prominently synthesized in often distinct areas of the central nervous system as documented by in situ hybridization. When co-expressed with alpha and beta subunits in Xenopus oocytes and mammalian cells, the gamma variants mediate the potentiation of GABA evoked currents by benzodiazepines and help generate high-affinity binding sites for these drugs. However, these sites show disparate pharmacological properties which, for receptors assembled from alpha 1, beta 1 and gamma 1 subunits, are characterized by the conspicuous loss in affinity for neutral antagonists (e.g. flumazenil) and negative modulators (e.g. DMCM). These findings reveal a pronounced effect of gamma subunit variants on GABAA/benzodiazepine receptor pharmacology.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Brain/metabolism Cattle Cloning, Molecular DNA/genetics,isolation & purification Gene Library Genetic Variation Humans Macromolecular Substances Molecular Sequence Data Nucleic Acid Hybridization Oligonucleotide Probes RNA, Messenger/analysis,genetics Rats Receptors, GABA-A/genetics,metabolism Recombinant Proteins/metabolism Sequence Homology, Nucleic Acid
Chemicals
Macromolecular Substances Oligonucleotide Probes RNA, Messenger Receptors, GABA-A Recombinant Proteins DNA
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ymer S
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, FRG.
Draguhn A
Wisden W
Werner P
Keinänen K
Schofield P R
Sprengel R
Pritchett D B
Seeburg P H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-10-00
Pages
3261-7
Language
English
Region
England
NLM ID
8208664
PMCID
PMC552059
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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