Ghorbel Mohamed T, Becker Kevin G, Henley Jeremy M
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, United Kingdom.
Physiol Genomics. 2005 Jun 16;22(1):93-8. doi: 10.1152/physiolgenomics.00202.2004. Epub 2005 Mar 22.
Metabotropic gamma-aminobutyric acid receptors (GABA(B)Rs) play a critical role in inhibitory synaptic transmission in the hippocampus. However, little is known about a possible long-term effect requiring transcriptional changes. Here, using microarray technology and RT-PCR of RNA from cultured rat embryonic hippocampal neurones, we report the profile of genes that are up- or downregulated by activation of GABA(B)Rs by baclofen but are not changed by baclofen in the presence of the GABA(B)R antagonist CGP-55845A. Our data show, for the first time, regulation of transcription of defined mRNAs after specific GABA(B) receptor activation. The identified genes can be grouped into those encoding signal transduction, endocytosis/trafficking, and structural classes of proteins. For example, butyrylcholinesterase, brain-derived neurotrophic factor, and COPS5 (Jab1) genes were upregulated, whereas Rab8 interacting protein and Rho GTPase-activating protein 4 were downregulated. These results provide important baseline genomic data for future studies aimed at investigating the long-term effects of GABA(B)R activation in neurones such as their roles in neuronal growth, pathway formation and stabilization, and synaptic plasticity.
代谢型γ-氨基丁酸受体（GABA(B)Rs）在海马体的抑制性突触传递中起关键作用。然而，对于可能需要转录变化的长期影响知之甚少。在此，我们利用微阵列技术以及对培养的大鼠胚胎海马神经元的RNA进行逆转录聚合酶链反应（RT-PCR），报告了由巴氯芬激活GABA(B)Rs而上调或下调，但在存在GABA(B)R拮抗剂CGP-55845A时不受巴氯芬影响的基因谱。我们的数据首次显示了特定GABA(B)受体激活后特定mRNA转录的调控情况。所鉴定的基因可分为编码信号转导、内吞作用/运输和蛋白质结构类别的基因。例如，丁酰胆碱酯酶、脑源性神经营养因子和COPS5（Jab1）基因上调，而Rab8相互作用蛋白和Rho GTP酶激活蛋白4下调。这些结果为未来旨在研究GABA(B)R激活在神经元中的长期影响（如它们在神经元生长、通路形成和稳定以及突触可塑性中的作用）的研究提供了重要的基础基因组数据。
