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Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors.
Author(s) -
Ymer S.,
Draguhn A.,
Wisden W.,
Werner P.,
Keinänen K.,
Schofield P. R.,
Sprengel R.,
Pritchett D. B.,
Seeburg P. H.
Publication year - 1990
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1990.tb07525.x
Subject(s) - gabaa receptor , biology , protein subunit , receptor , benzodiazepine , gamma subunit , neuroscience , genetics , computational biology , gene
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.