Department of Pharmacology, Kawasaki Medical School, Matsushima 577, Kurashiki 701-0192, Japan.
Synapse. 2013 Jan;67(1):51-5. doi: 10.1002/syn.21610. Epub 2012 Oct 16.
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.
虽然 1,4,5-三磷酸肌醇受体（IP3Rs-1）是调节细胞内 Ca2+浓度的主要钙通道之一，但关于其表达如何被长期乙醇暴露所修饰的相关数据却很少。本研究通过使用鼠大脑皮质神经元，尝试阐明长期乙醇暴露期间 GABA 受体（GABAARs）如何修饰 IP3R-1 表达。长期乙醇暴露会导致 IP3R-1 蛋白表达上调，同时其 mRNA 表达增加。使用选择性 GABAAR 激动剂 muscimol 预处理可显著抑制乙醇诱导的 IP3R-1 蛋白及其 mRNA 的上调，而选择性 GABAAR 拮抗剂 bicuculline 则可显著消除这种上调作用。这些结果表明，GABAAR 通过抑制基因转录来负调控乙醇诱导的 IP3R-1 蛋白表达上调。
