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

  title={The role of transcriptional and translational mechanisms in flumazenil-induced up-regulation of recombinant GABAA receptors},
  author={Maja Jazvin{\vs}{\'c}ak Jembrek and Dubravka {\vS}vob {\vS}trac and Josipa Vlaini{\'c} and Danka Peri{\vc}i{\'c}},
  journal={Neuroscience Research},
Zolpidem withdrawal induced uncoupling of GABA(A) receptors in vitro associated with altered GABA(A) receptor subunit mRNA expression.
An insight is provided into molecular and cellular mechanisms probably underlying adaptive changes of GABAA receptor function in response to chronic usage and withdrawal of zolpidem and perhaps the observed molecular changes could be linked to the tolerance and dependence produced upon prolonged treatment with other GABAergic drugs.
The effects of zolpidem treatment and withdrawal on the in vitro expression of recombinant α1β2γ2s GABAA receptors expressed in HEK 293 cells
In vitro studies suggest that a 2-day exposure of recombinant α1 subunit-containing GABAA receptors stably transfected in HEK 293 cells to zolpidem induces adaptive changes in this selective GabAA receptor subtype, which are not substantially different from those obtained after prolonged exposure of cells to high concentrations of diazepam.
GABA Receptors: Pharmacological Potential and Pitfalls.
The aim of this review is to briefly summarize the key pharmacological properties of GABA receptors, and to present selected novel findings with the potential to open new perspectives in the development of more effective therapeutic strategies.
Modulation of Recombinant GABAA Receptors by Neurosteroid Dehydroepiandrosterone Sulfate
The findings that prolonged DHEAS treatment does not produce changes in GABA<sub>A</sub> receptor expression and functional coupling, assumed to underlie the development of tolerance and dependence, might have importance in the long-term therapy necessary for the observed beneficial effects of D HEAS.
The role of flumazenil in the treatment of benzodiazepine dependence: physiological and psychological profiles
Low-dose flumazenil infusion appears to be a safe and effective treatment resulting in withdrawal symptoms of lesser severity than any other cessation method currently available.
Bioinformatics Analysis of Potential Biomarkers and Pathway Identification for Major Depressive Disorder
  • Dong Qi, Kui Chen
  • Biology
    Computational and mathematical methods in medicine
  • 2021
It was obtained that hypoxia, epithelial-mesenchymal transition, hedgehog signaling, and reactive oxygen species pathway were the enriched pathways for MDD patients.


Chronic flumazenil alters GABA(A) receptor subunit mRNA expression, translation product assembly and channel function in neuronal cultures.
Double-immunolabeling experiments using 5- and 10-nm gold particles suggest that after chronic flumazenil treatment, receptor subunit assemblies containing the alpha1/gamma2 and alpha6/delta subunits may be replaced by a receptor assembly containing thealpha1/d delta subunits.
Benzodiazepine Treatment Causes Uncoupling of Recombinant GABAA Receptors Expressed in Stably Transfected Cells
The uncoupling observed in this system was not accompanied by receptor internalization, is unlikely to be due to changes in receptor subunit composition, and probably represents posttranslational changes, and the rapid regulation of allosteric coupling by benzodiazepine treatment of the stably transfected cells should provide insights to the mechanisms of coupling between GABAA and benzodiazine receptors as well as benzODiazepine tolerance.
Mechanisms of up-regulation of D2L dopamine receptors by agonists and antagonists in transfected HEK-293 cells.
Results of experiments with cycloheximide, a protein-synthesis inhibitor, suggest that increased protein synthesis, and not decreased protein degradation, is responsible for up-regulation by both NPA and (-)-sulpiride.
Chronic benzodiazepine treatment of cells expressing recombinant GABAA receptors uncouples allosteric binding: studies on possible mechanisms
Mutation of the only PKAosphorylation site expressed from among the subunits proved that direct phosphorylation of the GABAR was not involved in either coupling after chronic BZ exposure or reversal of uncoupling after exposure to the competitive BZ antagonist, flumazenil.