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人肠道细胞系中的天然存在的胰高血糖素样肽-2(GLP-2)受体。

Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines.

作者信息

Sams Anette, Hastrup Sven, Andersen Marie, Thim Lars

机构信息

Departments of Molecular Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.

出版信息

Eur J Pharmacol. 2006 Feb 17;532(1-2):18-23. doi: 10.1016/j.ejphar.2005.12.001. Epub 2006 Jan 31.

Abstract

Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth.

摘要

尽管目前正在进行GLP - 2受体激动剂的临床试验,但GLP - 2诱导肠道上皮生长背后的机制仍有待了解。为了探究GLP - 2的作用机制,本研究旨在鉴定内源性表达GLP - 2受体的肠道细胞系。在此,我们报告首次鉴定出一种内源性表达功能性GLP - 2受体的细胞系。人肠道上皮细胞系FHC表达编码GLP - 2受体的mRNA(逆转录聚合酶链反应)和GLP - 2受体蛋白(蛋白质免疫印迹法)。在培养的FHC细胞中,GLP - 2诱导浓度依赖性的环磷酸腺苷(cAMP)积累(半数有效浓度的负对数pEC(50)=9.7±0.04(平均值±标准误,n = 4))。此外,还鉴定出一种天然存在的人肠道成纤维细胞系18Co,其可内源性表达编码GLP - 2受体的mRNA(逆转录聚合酶链反应)和蛋白(蛋白质免疫印迹法)。但在18Co细胞中未证实有受体功能(结合或G蛋白信号传导)。所鉴定出的与肠道相关的细胞系为未来阐明GLP - 2诱导上皮生长的潜在机制提供了工具。

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