Cell-specific extracellular signal-regulated kinase activation by multiple G protein-coupled receptor families in hippocampus
Cell-specific extracellular signal-regulated kinase activation by multiple G protein-coupled receptor families in hippocampus
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DOI：
10.1124/mol.63.1.128
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发表时间：
2003-01-01
影响因子：
3.6
通讯作者：
Levey, AI
中科院分区：
文献类型：
--
作者：
Berkeley, JL;Levey, AI
已显示几个G蛋白偶联受体（GPCR）家族在转染的细胞和非神经元系统中激活细胞外信号调节激酶（ERK）。然而，关于GPCR激活ERK在脑中的作用知之甚少。由于ERK是调节突触可塑性的重要组成部分，在这项研究中，我们研究了ERK激活的三个家庭的GPCR，在海马中的主要神经调节神经递质。我们用免疫细胞化学方法研究了毒蕈碱乙酰胆碱（mAChR），代谢型谷氨酸（mGluR）和β-肾上腺素能（β-AR）受体在小鼠海马脑片CA 1区神经元ERK激活。由于这些GPCR家族包含与每个主要异源三聚体G蛋白偶联的受体，我们研究了ERK激活是否根据G蛋白偶联而不同。通过使用免疫细胞化学，我们不仅能够检查每个受体家族是否激活ERK，而且还可以检查激活的ERK的细胞群和亚细胞分布。我们证明，M-1 mAChR和I组mGluR，这两者都是G（q）-偶联受体，激活ERK在CA 1锥体神经元，虽然激活响应mAChR是更强大的。G（i/o）偶联的II组mGluRs激活散布在整个CA 1的神经胶质中的ERK，G（s）偶联的β-AR受体激活散布在中间神经元中的ERK。因此，我们证明了GPCR与G（q）、G（i/o）和G（s）的偶联都激活海马中的ERK，尽管每种都具有独特的性质和分布。
Several families of G protein-coupled receptors (GPCR) have been shown to activate extracellular signal-regulated kinase (ERK) in transfected cells and non-neuronal systems. However, little is known about GPCR activation of ERK in brain. Because ERK is an important component in the regulation of synaptic plasticity, in this study we examined ERK activation by three families of GPCR that respond to major neuromodulatory neurotransmitters in the hippocampus. We used an immunocytochemical approach to examine ERK activation by muscarinic acetylcholine (mAChR), metabotropic glutamate (mGluR), and beta-adrenergic (beta-AR) receptors in CA1 neurons of mouse hippocampal slices. Because these GPCR families comprise receptors coupling to each of the major heterotrimeric G proteins, we examined whether ERK activation differs according to G-protein coupling. By using immunocytochemistry, we were able to examine not only whether each family of receptors activates ERK, but also the cellular populations and subcellular distributions of activated ERK. We demonstrated that M-1 mAChRs and group I mGluRs, both of which are G(q)-coupled receptors, activate ERK in CA1 pyramidal neurons, although activation in response to mAChR is more robust. The G(i/o)-coupled group II mGluRs activate ERK in glia scattered throughout CA1, and G(s)-coupled beta-AR receptors activate ERK in scattered interneurons. Thus, we demonstrated that GPCR coupling to G(q),G(i/o), and G(s) all activate ERK in the hippocampus, although each does so with unique properties and distributions.