Naslov
Prolonged exposure to gamma-aminobutyric acid up-regulates stably expressed recombinant alpha1 beta2 gamma2s GABA A receptors

Autori
Peričić, Danka ; Švob Štrac, Dubravka ; Jazvinšćak Jembrek, Maja ; Rajčan, Ivana

Izvornik
European Journal of Pharmacology (0014-2999) 482 (2003); 117-125

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
GABA A receptor; HEK 293 cells; gama-aminobutyric acid; Diazepam; Muscimol; Radioligand binding
(GABA A receptor; HEK 293 cells; gamma-aminobutyric acid; Diazepam; Muscimol; Radioligand binding)

Sažetak
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 alpha1 beta2 gamma2s GABA A receptors to gamma-aminobutyric (GABA, 1 mM) and muscimol (100 microM), but not to diazepam (1 microM), enhanced the maximum number (Bmax) of [3H]flunitrazepam binding sites without affecting their affinity (Kd). The GABA-induced enhancement in Bmax was reduced by the GABA receptor antagonist, bicuculline (100 microM), and by cycloheximide (10 microl/ml), a protein synthesis inhibitor. GABA (100 microM) 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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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