Increase in expression of the GABA(A) receptor alpha(4) subunit gene induced by withdrawal of, but not by long-term treatment with, benzodiazepine full or partial agonists
| Autor: | Elisabetta Cagetti, Mario Carta, Luisa Mancuso, Francesca Biggio, Enrico Sanna, Fabio Busonero, Maria Speranza Desole, Federico Massa, Paolo Follesa, Annalisa Manca, Elisabetta Maciocco, Giovanni Biggio |
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| Rok vydání: | 2001 |
| Předmět: |
Flumazenil
medicine.medical_specialty Cerebellum Microinjections medicine.drug_class Substance-Related Disorders Nerve Tissue Proteins Biology Partial agonist Membrane Potentials GABA Antagonists Cellular and Molecular Neuroscience Benzodiazepines Xenopus laevis Chlorides Chloride Channels Internal medicine medicine Animals GABA-A Receptor Agonists GABA-A Receptor Antagonists RNA Messenger Receptor Molecular Biology GABA Agonists Cells Cultured Neurons Benzodiazepine Diazepam Ion Transport GABAA receptor Cell Membrane Imidazoles Long-term potentiation Imidazenil Drug Tolerance Receptors GABA-A Rats Substance Withdrawal Syndrome Up-Regulation Protein Subunits Endocrinology medicine.anatomical_structure Anti-Anxiety Agents Oocytes Female medicine.drug |
| Zdroj: | Brain research. Molecular brain research. 92(1-2) |
| ISSN: | 0169-328X |
| Popis: | The effects of long-term exposure to, and subsequent withdrawal of, diazepam or imidazenil (full and partial agonists of the benzodiazepine receptor, respectively) on the abundance of GABA(A) receptor subunit mRNAs and peptides were investigated in rat cerebellar granule cells in culture. Exposure of cells to 10 microM diazepam for 5 days significantly reduced the amounts of alpha(1) and gamma(2) subunit mRNAs, and had no effect on the amount of alpha(4) mRNA. These effects were accompanied by a decrease in the levels of alpha(1) and gamma(2) protein and by a reduction in the efficacy of diazepam with regard to potentiation of GABA-evoked Cl- current. Similar long-term treatment with 10 microM imidazenil significantly reduced the abundance of only the gamma(2)S subunit mRNA and had no effect on GABA(A) receptor function. Withdrawal of diazepam or imidazenil induced a marked increase in the amount of alpha(4) mRNA; withdrawal of imidazenil also reduced the amounts of alpha(1) and gamma(2) mRNAs. In addition, withdrawal of diazepam or imidazenil was associated with a reduced ability of diazepam to potentiate GABA action. These data give new insights into the different molecular events related to GABA(A) receptor gene expression and function produced by chronic treatment and withdrawal of benzodiazepines with full or partial agonist properties. |
| Databáze: | OpenAIRE |
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