Nasser Yasmin, Keenan Catherine M, Ma Adrienne C, McCafferty Donna-Marie, Sharkey Keith A
Institute for Infection, Immunity and Inflammation, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.
Glia. 2007 Jun;55(8):859-72. doi: 10.1002/glia.20507.
The metabotropic glutamate receptor 5 (mGluR5) is expressed by astrocytes and its expression is modulated by inflammation. Enteric glia have many similarities to astrocytes and are the most numerous cell in the enteric nervous system (ENS). We investigated whether enteric glia express a functional mGluR5 and whether expression of this receptor was altered in colitis. In both enteric plexuses of the ileum and colon of guinea pigs and mice, we observed widespread glial mGluR5 expression. Incubation of isolated segments of the guinea pig ileum with the mGluR5 specific agonist RS-2-chloro-5-hydroxyphenylglycine (CHPG) caused a dose-dependent increase in the glial expression of c-Fos and the phosphorylated form of the extracellular signal-regulated kinase 1/2. Preincubation of tissues with the group I metabotropic glutamate receptor antagonist, S-4-carboxyphenylglycine, abolished the effects of CHPG. We examined mGluR5 expression in the guinea pig trinitrobenzene sulfonic acid and the IL-10 gene-deficient (IL-10(-/-)) mouse models of colitis. In guinea pigs, mGluR5 immunoreactivity became diffusely localized over the colonic myenteric ganglia, suggesting a change in receptor distribution. In contrast, glial mGluR5 expression was significantly reduced in the colonic myenteric plexus of IL-10(-/-) mice, as assessed with both real-time quantitative RT-PCR as well as immunohistochemistry and image analysis. These changes occurred without concomitant changes to enteric ganglia or glial fibrillary acidic protein expression in the IL-10(-/-) mouse. Our data suggest that enteric glia are a functional target of the glutamatergic neurotransmitter system in the ENS and that changes in mGluR5 expression may be of physiological significance during colitis.
代谢型谷氨酸受体5（mGluR5）由星形胶质细胞表达，其表达受炎症调节。肠胶质细胞与星形胶质细胞有许多相似之处，是肠神经系统（ENS）中数量最多的细胞。我们研究了肠胶质细胞是否表达功能性mGluR5，以及该受体的表达在结肠炎中是否发生改变。在豚鼠和小鼠回肠及结肠的两个肠神经丛中，我们均观察到胶质细胞广泛表达mGluR5。用mGluR5特异性激动剂RS-2-氯-5-羟基苯甘氨酸（CHPG）孵育豚鼠回肠分离段，可导致胶质细胞中c-Fos和细胞外信号调节激酶1/2磷酸化形式的表达呈剂量依赖性增加。用I组代谢型谷氨酸受体拮抗剂S-4-羧基苯甘氨酸对组织进行预孵育，可消除CHPG的作用。我们检测了豚鼠三硝基苯磺酸和白细胞介素10基因缺陷（IL-10(-/-)）小鼠结肠炎模型中的mGluR5表达。在豚鼠中，mGluR5免疫反应性弥漫性定位于结肠肌间神经节，提示受体分布发生改变。相比之下，通过实时定量逆转录聚合酶链反应以及免疫组织化学和图像分析评估，IL-10(-/-)小鼠结肠肌间神经丛中的胶质细胞mGluR5表达显著降低。这些变化在IL-10(-/-)小鼠中并未伴随肠神经节或胶质纤维酸性蛋白表达的改变。我们的数据表明，肠胶质细胞是ENS中谷氨酸能神经递质系统的功能性靶点，mGluR5表达的变化在结肠炎期间可能具有生理意义。
