Chronic exposure of cells expressing recombinant GABAA receptors to benzodiazepine antagonist flumazenil enhances the maximum number of benzodiazepine binding sites.

The aim of this study was to better understand the mechanisms that underlie adaptive changes in GABAA receptors following their prolonged exposure to drugs. Exposure (48 h) of human embryonic kidney (HEK) 293 cells stably expressing recombinant alpha1beta2gamma2S GABAA receptors to flumazenil (1 or 5 microM) in the presence of GABA (1 microM) enhanced the maximum number (Bmax) of [3H]flunitrazepam binding sites without affecting their affinity (Kd). The flumazenil-induced enhancement in Bmax was not counteracted by diazepam (1 microM).

Prolonged exposure to gamma-aminobutyric acid up-regulates stably expressed recombinant alpha 1 beta 2 gamma 2s GABAA receptors.

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 alpha1beta2gamma2s GABA(A) receptors for gamma-aminobutyric (GABA, 1 mM) and muscimol (100 microM), but not for diazepam (1 microM), 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 microM), and by cycloheximide (10 microl/ml), a protein synthesis inhibitor.