Abstract
The aim of this study was to better understand the mechanisms that underlie adaptive changes in GABA A receptors following their prolonged exposure to drugs. Exposure (48 and/or 96 h) of human embryonic kidney (HEK 293) cells stably expressing recombinant α1β2γ2s GABA A receptors for γ-aminobutyric (GABA, 1 mM) and muscimol (100 μM), but not for diazepam (1 μM), enhanced the maximum number ( B max) of [ 3H]flunitrazepam binding sites without affecting their affinity ( K d). The GABA-induced enhancement in B max was reduced by the GABA receptor antagonist, bicuculline (100 μM), and by cycloheximide (10 μl/ml), a protein synthesis inhibitor. GABA (100 μM) enhanced the affinity of [ 3H]flunitrazepam binding to vehicle- and GABA-pretreated, but not to diazepam-pretreated, HEK 293 cells. The results suggest that chronic GABA treatment up-regulates stably expressed GABA A receptors, presumably by stimulating their synthesis. Unlike chronic diazepam, which produced functional uncoupling of GABA and benzodiazepine binding sites, chronic GABA failed to produce this effect.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.