Regulation of ion transpot by short chain fatty acids receptor, GPR43 in colonic epithelia

结肠上皮中短链脂肪酸受体 GPR43 对离子转运的调节

• 批准号: 18590207
• 负责人: KUWAHARA Atsukazu
• 金额: $ 2.57万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590207/
• 关键词: short chain fatty acid; G protein coupled receptor; colonic function; inn transnnrt; dietary fiber; intestinal motility; chemosensory; epithelium; 大腸運動

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are the major anions in the large intestinal lumen. They are produced from dietary fiber by bacterial fermentation and are known to have a variety of physiological and pathophysiological effects on the intestine.In the present study, I have investigated (1) the expression of SCFA receptor, GPR43 in the rat and human colon and (2) the regulation of ion transport in rat colonic mucosa. Expression of GPR43 was detected by reverse transcriptase/polymerase chain reaction (RT PCR), western blotting, and immunohistochemistry. mRNA for GPR43 was detected, by RT-PCR, in extracts of the whole wall and separated mucosa from the ileum and colon and from muscle plus submucosa from the ileum, but not from muscle plus submucosa preparation from the rat and human colon. I have also made specific GPR43 antiserum. GPR43 protein was detected by western blot analysis in extract of whole wall and separated mucosa, but not in muscle plus submucosa extracts. By immunohistochemistry, GPR43 immunoreactivity was localized to enteroendocrine cells expressing peptide YY (PYY), whereas 5-HT-immunoreactive enteroendocrine cells were not immunoreactive for GPR43. Mast cells of the lamina propria expressing 5-HT were also GPR43 immunoreactive. The results of the present study suggest that the PYY-containing enteroendocrine cells and 5-HT-containing mucosal mast cells sense SCFAs via GPR43 receptor.In the physiological study, mucosal addition of SCFAs evoked increases in short circuit current in a concentration-dependent manner. The responses were inhibited by neuronal blocker tetrodotoxin. These molecular biological and physiological studies suggest that GPR 43 senses luminal SCFA and induces ion transport in the colon. Therefore, GPR43 has an important role to regulate colonic functions.

短链脂肪酸（SCFA），例如乙酸盐，丙酸和丁酸酯，是大肠腔中的主要阴离子。它们是通过细菌发酵由饮食纤维产生的，已知它们对肠有多种生理和病理生理作用。在本研究中，我研究了（1）（1）SCFA受体在大鼠和人类结肠中的GPR43的表达，以及（2）（2）（2）（2）在Rat Colonic Mucosa中的离子转运。通过逆转录酶/聚合酶链反应（RT PCR），蛋白质印迹和免疫组织化学检测到GPR43的表达。 RT-PCR在整个壁的提取物中检测到GPR43的mRNA，并将粘膜与回肠和结肠分离，并从肌肉和肌肉中的粘胶中分离出来，但不能从肌肉和大鼠和人类结肠的肌肉和粘膜下的制剂中。我还制作了特定的GPR43抗血清。通过在整个壁和分离的粘膜提取物中，通过蛋白质印迹分析检测到GPR43蛋白，但在肌肉和粘膜下提取物中未检测到。通过免疫组织化学，将GPR43免疫反应性定位于表达肽YY（PYY）的肠内分泌细胞，而5-HT-免疫反应性肠内分泌细胞的GPR43并非免疫反应性。表达5-HT的椎板的肥大细胞也具有GPR43免疫反应性。本研究的结果表明，含PYY的肠肠内分泌细胞和5-HT的粘膜肥大细胞通过GPR43受体感测SCFA。在生理学研究，SCFA的粘膜添加在浓度依赖性方式的短路电流中诱发的SCFA添加。神经元阻滞剂四毒素抑制了反应。这些分子生物学和生理学研究表明，GPR 43感觉到腔内SCFA并在结肠中诱导离子转运。因此，GPR43在调节结肠功能方面具有重要作用。

项目成果

Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8

• DOI: 10.2220/biomedres.27.243
• 发表时间: 2006-10-01
• 期刊: BIOMEDICAL RESEARCH-TOKYO
• 影响因子: 1.2
• 作者: Iwanaga, Toshihiko;Takebe, Kumiko;Kuwahara, Atsukazu
• 通讯作者: Kuwahara, Atsukazu

大腸の水・電解質輸送調節機構-腸管神経系-内分泌系-免疫系およびプロスタグランジンの関与-

调节大肠中的水和电解质运输 - 肠神经系统 - 内分泌系统 - 免疫系统和前列腺素的参与 -

• 发表时间: 2007
• 期刊: GI.Research 15
• 作者: 山田勝也;他;唐木 晋一郎・桑原 厚和
• 通讯作者: 唐木 晋一郎・桑原 厚和

Effects of short-chain fatty acids on large intestinal motility and their mode of detection

短链脂肪酸对大肠蠕动的影响及其检测方法

• 发表时间: 2006
• 作者: Karaki;S.-I.;Mitsui;R.;Ono;S.;Tazoe;H.;Yajima;T.;Furness;J.B.;Kuwahara;A
• 通讯作者: A

Expression of the short-chain fatty acid receptor, GPR43, in human Colon

短链脂肪酸受体 GPR43 在人结肠中的表达

• 发表时间: 2008
• 期刊: Journal of Molecular Histology 38
• 作者: Karaki;S.-I.;Tazoe;H.;Hayashi;H.;Kashiwabara;H.;Tooyama;K.;Suzuki;Y. and Kuwahara;A
• 通讯作者: A

「研究成果報告書概要(和文)」より

摘自《研究结果报告摘要（日文）》

• 发表时间: 2005
• 作者: Kawauchi;et. al.;Nishimura et al.;Dezawa et al.;Yoshizawa et al.;星野 幹雄;星野 幹雄
• 通讯作者: 星野 幹雄