首页> 外文期刊>American Journal of Physiology >Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon.
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Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon.

机译:gustducin的α-亚基与PYY和GLP-1在人结肠L细胞中的共定位。

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摘要

In view of the importance of molecular sensing in the function of the gastrointestinal (GI) tract, we assessed whether signal transduction proteins that mediate taste signaling are expressed in cells of the human gut. Here, we demonstrated that the alpha-subunit of the taste-specific G protein gustducin (Galpha(gust)) is expressed prominently in cells of the human colon that also contain chromogranin A, an established marker of endocrine cells. Double-labeling immunofluorescence and staining of serial sections demonstrated that Galpha(gust) localized to enteroendocrine L cells that express peptide YY and glucagon-like peptide-1 in the human colonic mucosa. We also found expression of transcripts encoding human type 2 receptor (hT2R) family members, hT1R3, and Galpha(gust) in the human colon and in the human intestinal endocrine cell lines (HuTu-80 and NCI-H716 cells). Stimulation of HuTu-80 or NCI-H716 cells with the bitter-tasting compound phenylthiocarbamide, which binds hT2R38, induced a rapid increase in the intracellular Ca2+ concentration in these cells. The identification of Galpha(gust) and chemosensory receptors that perceive chemical components of ingested substances, including drugs and toxins, in open enteroendocrine L cells has important implications for understanding molecular sensing in the human GI tract and for developing novel therapeutic compounds that modify the function of these receptors in the gut.
机译:鉴于分子传感在胃肠道(GI)的功能中的重要性,我们评估了在人类肠道细胞中是否表达了介导味觉信号的信号转导蛋白。在这里,我们证明了味觉特异性G蛋白gustducin(Galpha(gust))的α亚基在还含有嗜铬粒蛋白A(已建立的内分泌细胞)的人类结肠细胞中显着表达。双重标记的免疫荧光法和连续切片染色表明,Galpha(gust)位于人结肠粘膜中表达肽YY和胰高血糖素样肽1的肠内分泌L细胞。我们还发现在人类结肠和人类肠内分泌细胞系(HuTu-80和NCI-H716细胞)中编码人类2型受体(hT2R)家族成员,hT​​1R3和Galpha(gust)的转录本表达。结合hT2R38的苦味化合物苯硫脲对HuTu-80或NCI-H716细胞的刺激诱导了这些细胞中细胞内Ca2 +浓度的快速增加。在开放性肠内分泌L细胞中识别感知摄入的物质(包括药物和毒素)的化学成分的Galpha(gust)和化学感应受体,对于理解人类胃肠道中的分子传感以及开发修饰功能的新型治疗化合物具有重要意义。这些受体在肠道中。

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