ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Benzodiazepines (BZDs), barbiturates, ethanol, and general anesthetics potentiate the action of γ-aminobutyric acid (GABA) at the type A GABA receptor (GABAAR) and have profound effects on mood, arousal, and susceptibility to seizures. GABAAR number and subunit mRNA levels change in animal models of epilepsy and anxiety and following exposure to GABAAR 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 GABAAR subunit isoforms, which form a receptor enhanced by nonselective BZDs. Down-regulation of α1 mRNA (t1/2 = 8 h) precedes down-regulation of receptor number (t1/2 = 25 h), suggesting that GABA-induced GABAAR 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 GABAAR subunit mRNA down-regulation is not a consequence of accelerated mRNA degradation and argue that GABA-induced GABAAR down-regulation is due to inhibition of transcription.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0741041.x
