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（SCFAs），如乙酸盐、丙酸盐和丁酸盐，是大肠内腔中的主要阴离子。它们是由膳食纤维通过细菌发酵产生的，并且已知对肠道具有多种生理和病理生理学作用。在本研究中，我研究了（1）大鼠和人结肠中SCFA受体GPR 43的表达和（2）大鼠结肠粘膜中离子转运的调节。采用逆转录聚合酶链反应（RT PCR）、免疫印迹和免疫组织化学方法检测GPR 43的表达。通过RT-PCR，在回肠和结肠的整个壁和分离的粘膜以及来自回肠的肌肉加粘膜下层的提取物中检测到GPR 43的mRNA，但在来自大鼠和人结肠的肌肉加粘膜下层制备物中未检测到GPR 43的mRNA。我还做了特异性GPR 43抗血清。免疫印迹分析显示，GPR 43蛋白在全壁和分离的粘膜提取物中检测到，但在肌肉和粘膜下层提取物中未检测到。通过免疫组织化学，GPR 43免疫反应定位于表达肽YY（PYY）的肠内分泌细胞，而5-HT免疫反应肠内分泌细胞对GPR 43没有免疫反应。肥大细胞的固有层表达5-HT也GPR 43免疫反应。本研究结果表明，含PYY的肠内分泌细胞和含5-HT的粘膜肥大细胞通过GPR 43受体感受SCFAs，在生理学研究中，粘膜加入SCFAs引起短路电流增加，并呈浓度依赖性。神经元阻断剂河豚毒素可抑制该反应。这些分子生物学和生理学研究表明，GPR 43感测管腔SCFA并诱导结肠中的离子转运。因此，GPR 43在调节结肠功能中具有重要作用。

项目成果

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

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

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

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

大腸の腸管神経系Entelic Nervous System-II.大腸運動調節、粘膜上皮における水・電解質輸送調節、および生体防御機構に対する関与-

大肠的肠神经系统-II。调节大肠运动、调节粘膜上皮中的水和电解质运输以及参与生物防御机制。

• 发表时间: 2008
• 期刊: FFI Journal 213
• 作者: Nishina S.;et. al.;唐木 晋一郎・桑原 厚和
• 通讯作者: 唐木 晋一郎・桑原 厚和