Lee Ki-Hwan, Ahn Joon-Ik, Yu Dong-Hyun, Koh Hyun Chul, Kim Seok Hyeon, Yang Byung Hwan, Lee Young Seek, Lee Yong-Sung
Department of Biochemistry, College of Medicine and The Mental Health Research Institute, Hanyang University, Seoul, Korea.
Int J Mol Med. 2003 May;11(5):559-68.
Dextromethorphan is a widely used anti-tussive drug with non-competitive antagonistic effects on excitatory amino acid receptors of the N-methyl-D-aspartate (NMDA) type. This study examined the effect of daily dextromethorphan administration on gene expression in rat brain hippocampus and cortex regions using Rat 5K cDNA microarrays. Triplicate microarray assays were performed at each time point (1, 3 and 10 days), and results were confirmed using semi-quantitative RT-PCR on a subset of differentially expressed cDNA. The microarray analysis proved able to detect changes in gene expression following dextromethorphan injection. Moreover, these changes were mostly mediated by an NMDA receptor. The hippocampus region showed more alterations in gene expression than cerebral cortex following dextromethorphan treatment. The expression of many glutamate-induced apoptosis-related genes, and NO-dependent apoptosis-associated genes, was down-regulated. Expression of anti-apoptotic genes, such as nucleophosmin/B23, Rab2, MAP kinase kinase and CREB binding protein, was up-regulated by dextromethorphan. Angiogenesis is likely to be inhibited in our system due to observed down-regulation of VEGF-associated genes. Expression of some SNARE genes was up-regulated in rat brain hippocampus and cortex regions after dextromethorphan injection.
右美沙芬是一种广泛使用的镇咳药，对N-甲基-D-天冬氨酸（NMDA）型兴奋性氨基酸受体具有非竞争性拮抗作用。本研究使用大鼠5K cDNA微阵列检测了每日给予右美沙芬对大鼠脑海马体和皮质区域基因表达的影响。在每个时间点（1天、3天和10天）进行了三次重复的微阵列分析，并使用半定量RT-PCR对一部分差异表达的cDNA进行了结果验证。微阵列分析证明能够检测到右美沙芬注射后基因表达的变化。此外，这些变化大多由NMDA受体介导。右美沙芬治疗后，海马体区域基因表达的变化比大脑皮质更多。许多谷氨酸诱导的凋亡相关基因和一氧化氮依赖性凋亡相关基因的表达下调。右美沙芬上调了抗凋亡基因的表达，如核仁磷酸蛋白/B23、Rab2、丝裂原活化蛋白激酶激酶和CREB结合蛋白。由于观察到VEGF相关基因的下调，我们的系统中血管生成可能受到抑制。右美沙芬注射后，大鼠脑海马体和皮质区域中一些SNARE基因的表达上调。
