Muscimol-induced reduction of GABAA receptor alpha 1-subunit mRNA in primary cultured cerebral cortical neurons.
The expression of mRNA for GABAA receptor alpha 1-subunit in mouse cerebral cortical neurons in primary culture was examined using RNA blot analysis and ribonuclease protection assay following the treatment of neurons with muscimol, a selective agonist of GABAA receptor. The level of mRNA for GABAA receptor alpha 1-subunit showed a decrease in comparison with that in non-treated cells, whereas no changes in the level of beta-actin mRNA were noted under the same experimental conditions. This muscimol-induced reduction in GABAA receptor alpha 1-subunit mRNA was counteracted by the simultaneous exposure of neurons to both bicuculline, an antagonist of GABAA receptor, and muscimol. The expression of mRNA for GABAA receptor alpha 1-subunit also showed a decline by the treatment of cells with flunitrazepam alone, an agonist of benzodiazepine receptor, and this change was also abolished by the simultaneous exposure of cells to flunitrazepam and Ro15-1788, an antagonist for central benzodiazepine receptor. These results suggest that the continuous stimulation of cerebral GABAA receptor complex may induce the reduced expression of mRNA for the receptor complex.
Hirouchi
M
M
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Ohkuma
S
S
Kuriyama
K
K
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005445:Flunitrazepam / Q000494:pharmacology; D051379:Mice; D009118:Muscimol / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics*; D012260:Ribonucleases
D010446:Peptide Fragments; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; D012260:Ribonucleases; D001640:Bicuculline