title: Activation of GABA(A)  receptors suppresses ethanol-induced upregulation of type 1 IP(3)  receptors.
abstract: Although Type 1 inositol 1,4,5-trisphosphate receptors (IP(3) Rs-1) are one of the major calcium channels to regulate intracellular Ca(2+) concentration, there have been few available data how their expression is modified by long-term exposure to ethanol. The present study attempted to clarify mechanisms of modification of IP(3) R-1 expression during long-term ethanol exposure by γ-aminobutyric acid (GABA)A receptors using mouse cerebral cortical neurons. Long-term exposure to ethanol induced IP(3) R-1 protein upregulation following increased expression of its mRNA. Pretreatment with muscimol, a selective GABA(A) receptor agonist, significantly suppressed the ethanol-induced upregulation of IP(3) R-1 protein and its mRNA, which was significantly abolished by bicuculline, a selective GABA(A) receptor antagonist. These results indicate that GABA(A) receptors negatively regulate the ethanol-induced upregulation of IP(3) R-1 protein expression via the suppression of gene transcription.
authors.affiliation: Department of Pharmacology, Kawasaki Medical School, Matsushima 577, Kurashiki 701-0192, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuno
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Seitaro
authors.initials: S
authors.lastname: Ohkuma
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; D001640:Bicuculline