Activation of GABA(A) receptors suppresses ethanol-induced upregulation of type 1 IP(3) receptors

• Published in: Synapse (New York, N.Y.) N.Y.), 2013-01, Vol.67 (1), p.51-55
• Main Authors: Mizuno, Koji, Kurokawa, Kazuhiro, Ohkuma, Seitaro
• Format: Article
• Language: English
• Subjects: Animals; Bicuculline - pharmacology; Cerebral Cortex - metabolism; Ethanol - pharmacology; GABA-A Receptor Agonists - pharmacology; GABA-A Receptor Antagonists - pharmacology; Inositol 1,4,5-Trisphosphate Receptors - genetics; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Mice; Muscimol - pharmacology; Neurons - metabolism; Receptors, GABA-A - metabolism; RNA, Messenger - biosynthesis; Transcription, Genetic - drug effects; Up-Regulation - drug effects
• ISSN: 1098-2396
• DOI: 10.1002/syn.21610

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.