engleski

Enhancement of benzodiazepine binding sites following chronic treatment with flumazenil

The aim of this study was to improve our knowledge of the mechanisms leading to adaptive changes in gamma-aminobutyric acid A (GABA-A) receptors following chronic drug treatment. Exposure (48 h) of human embryonic kidney (HEK 293) cells stably expressing recombinant alpha1 beta2 gamma2S GABA-A receptors to the antagonist of benzodiazepine binding sites, flumazenil (5 microM), enhanced the maximum number (Bmax) and the equilibrium dissociation constant (Kd) of [3H]flunitrazepam binding sites. The flumazenil-induced enhancement in Bmax was potentiated by GABA (50 microM), and reduced by the GABA-A receptor antagonist, bicuculline (100 microM). Flumazenil-induced enhancement in Kd was affected by neither of these treatments. GABA (50 microM) enhanced the density of [3H]flunitrazepam binding sites, and this enhancement was greater in the presence of diazepam (1 microM). The results suggest that chronic flumazenil treatment up-regulates in a bicuculline sensitive manner benzodiazepine binding sites at stably expressed GABA-A receptors.

GABA-A receptor; HEK 293 cell; Flumazenil; Diazepam; GABA (gamma-aminobutyric acid); [3H]flunitrazepam binding

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