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Turnover and Down‐Regulation of GABA A Receptor α1, β2S, and γ1 Subunit mRNAs by Neurons in Culture
Author(s) -
Lyons Helen R.,
Gibbs Terrell T.,
Farb David H.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741041.x
Subject(s) - gabaa receptor , gaba receptor , gamma aminobutyric acid , receptor , protein subunit , messenger rna , gene isoform , biology , gabaa rho receptor , endocrinology , medicine , interleukin 5 receptor alpha subunit , chemistry , g alpha subunit , biochemistry , gene
Abstract: Benzodiazepines (BZDs), barbiturates, ethanol, and general anesthetics potentiate the action of γ‐aminobutyric acid (GABA) at the type A GABA receptor (GABA A R) and have profound effects on mood, arousal, and susceptibility to seizures. GABA A R number and subunit mRNA levels change in animal models of epilepsy and anxiety and following exposure to GABA A R agonists and positive modulators, but the mechanism of receptor down‐regulation remains unknown. Persistent exposure (48 h) of brain neurons in primary culture to GABA results in a 30% decrease in the levels of mRNA encoding the α1, β2S, and γ1 GABA A R subunit isoforms, which form a receptor enhanced by nonselective BZDs. Down‐regulation of α1 mRNA ( t 1/2 = 8 h) precedes down‐regulation of receptor number ( t 1/2 = 25 h), suggesting that GABA‐induced GABA A R down‐regulation is a consequence of decreased mRNA levels. The apparent half‐life of the α1 mRNA in the presence of α‐amanitin (9 h) is consistent with the time course of α1 mRNA down‐regulation. Moreover, the stability of the α1, β2S, and γ1 subunit mRNAs is not altered by chronic GABA exposure. The results demonstrate that GABA A R subunit mRNA down‐regulation is not a consequence of accelerated mRNA degradation and argue that GABA‐induced GABA A R down‐regulation is due to inhibition of transcription.