title: Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors.
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.
authors.affiliation: Laboratory of Molecular Neuroendocrinology, University of Heidelberg, FRG.
authors.forename: S
authors.initials: S
authors.lastname: Ymer
authors.forename: A
authors.initials: A
authors.lastname: Draguhn
authors.forename: W
authors.initials: W
authors.lastname: Wisden
authors.forename: P
authors.initials: P
authors.lastname: Werner
authors.forename: K
authors.initials: K
authors.lastname: Keinänen
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
authors.forename: R
authors.initials: R
authors.lastname: Sprengel
authors.forename: D B
authors.initials: DB
authors.lastname: Pritchett
authors.forename: P H
authors.initials: PH
authors.lastname: Seeburg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D014644:Genetic Variation; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D004247:DNA