The role of transcriptional and translational mechanisms in flumazenil-induced up-regulation of recombinant GABA_A receptors

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• 作者：Maja Jazvin&#x161 ; ć ; ak Jembrek ; Dubravka &#x160 ; vob &#x160 ; trac ; Josipa Vlainić ; Danka Perič ; ić
• 关键词：Chronic flumazenil ; GABA_A receptor ; Recombinant ; HEK 293 cells ; Inhibitors of RNA and protein synthesis ; [³H]muscimol and [³H]flunitrazepam binding ; ; //www.sciencedirect.com/scidirimg/entities/204e.gif"" alt=""
• 刊名：Neuroscience Research
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：61
• 期：3
• 页码：234-241
• 全文大小：371 K

文摘

The aim of this study was to further elucidate the mechanisms involved in adaptive changes of GABA_A receptors following prolonged exposure to flumazenil, the antagonist of benzodiazepine binding sites on GABA_A receptors. The effects of prolonged flumazenil treatment were studied on recombinant ₁β₂γ_2S GABA_A receptors stably expressed in human embryonic kidney (HEK 293) cells. Using radioligand binding experiments we found enhancement in the maximum number of [³H]muscimol labeled binding sites in different preparations of HEK 293 cells. The parallel increase of [³H]flunitrazepam binding sites in the membranes was reduced in the presence of actinomycin D and cycloheximide, inhibitors of RNA and protein synthesis, respectively. Chronic flumazenil also raised the steady-state level of mRNA encoding ₁ receptor subunit. The results suggest that the up-regulation of GABA_A receptors, observed after prolonged flumazenil treatment is at least partly due to increased de novo synthesis of receptor proteins at both transcriptional and translational level.