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

• Project/Area Number: 18590207
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: University of Shizuoka
• Principal Investigator: KUWAHARA Atsukazu University of Shizuoka, Institute for Environmental Sciences, professor (60142890)
• Co-Investigator(Kenkyū-buntansha): KARAKI Shin-ichirou University of Shizuoka, Institute for Environmental Sciences, professor (00363903)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: short chain fatty acid / G protein coupled receptor / colonic function / inn transnnrt / dietary fiber / intestinal motility / chemosensory / epithelium / 大腸運動

Research Abstract

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.

Research Products

• [Journal Article] Expression of the short-chain fatty acid receptol,GPR43,in human colon (2008)
  • Author(s): Karaki, S.-I., Tazoe, H., Hayashi, H.Kashiwabara, H., Tooyama, K., Suzuki, Y.and Kuwahara, A
  • Journal Title: Journal of Molecular Histology 38 Pages: 135-142
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglaindins,sensory afferent neuropeptides and nitric oxides (2008)
  • Author(s): Brzozowski, T., Konturek, P.C., Sliwowski, Z., Drozdowicz, D., Burnat, G, Pajdo, R., Pawlik, M., Bielanski, W., Kato, I., Kuwahara, A., Konturek, S.J.and Pawlik, W.W
  • Journal Title: Regulatory peptides Available online 20,Feb
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 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- (2008)
  • Author(s): 唐木 晋一郎・桑原 厚和
  • Journal Title: FFI Journal 213 Pages: 157-168
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Expression of the short-chain fatty acid receptor, GPR43, in human Colon (2008)
  • Author(s): Karaki, S.-I., Tazoe, H., Hayashi, H., Kashiwabara, H., Tooyama, K., Suzuki, Y. and Kuwahara, A
  • Journal Title: Journal of Molecular Histology 38 Pages: 135-142
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of the short-chain fatty acid receptor, GPR43, in human colon (2008)
  • Author(s): Karaki, S.-I., Tazoe, H., Hayashi, H. Kashiwabara, H., Tooyama, K., Suzuki, Y. and Kuwahara, A.
  • Journal Title: Journal of Molecular Histology 38 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglaindins, sensory afferent neuropeptides and nitric oxides (2008)
  • Author(s): Brzozowski, T., Konturek, P. C., Sliwowski, Z., Drozdowicz, D., Burnat, G., Pajdo, R., Pawlik, M., Bielanski, W., Kato, I., Kuwahara, A., Konturek, S. J. and Pawlik, W. W.
  • Journal Title: Regulatory peptides Available online 20, Feb,
  • Peer Reviewed
• [Journal Article] 大腸の腸管神経系Enteric 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- (2008)
  • Author(s): 唐木晋一郎・桑原厚和
  • Journal Title: FFI Journal 213 Pages: 157-168
  • Peer Reviewed
• [Journal Article] The tight junction component protein,claudin-4,is expressed by enteric neurons in the rat distal colon (2007)
  • Author(s): Kairki, S.-I., Kaji, I., Otomo, Y., Tazoe, H.and Kuwahara, A
  • Journal Title: Neuroscience Letters 428 Pages: 88-92
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 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- (2007)
  • Author(s): 唐木 晋一郎・桑原 厚和
  • Journal Title: GI.Research 15 Pages: 43-53
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 大腸の腸管神経系Entedc Nervous System-I.腸管神経細胞の形態・機能的分類と神経回路- (2007)
  • Author(s): 唐木 晋一郎・桑原 厚和
  • Journal Title: FFI Journal 212 Pages: 1044-1053
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon (2007)
  • Author(s): Kairki, S. -I., Kaji, I., Otomo, Y., Tazoe, H. and Kuwahara, A.
  • Journal Title: Neuroscience Letters 428 Pages: 88-92
  • Peer Reviewed
• [Journal Article] 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- (2007)
  • Author(s): 唐木晋一郎・桑原厚和
  • Journal Title: G. I. Research 15 Pages: 43-53
  • Peer Reviewed
• [Journal Article] 大腸の腸管神経系Enteric Nervous System-I.腸管神経細胞の形態・機能的分類と神経回路- (2007)
  • Author(s): 唐木晋一郎・桑原厚和
  • Journal Title: FFI Journal 212 Pages: 1044-1053
  • Peer Reviewed
• [Journal Article] Fibre-free diet leads to impairment of neuronally mediated muscle Contractile response in rat distal colon (2006)
  • Author(s): Mitsui, R., Karaki, S.-I., Kubo, Y., Sugiura, Y., Kuwahara, A
  • Journal Title: Neurogastroenterology & Motility 18 Pages: 1093-1101
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8 (2006)
  • Author(s): Iwanaga, T., Takebe, K., Kato, I., Karaki, S., Kuwahara, A
  • Journal Title: Biomedical Research 27 Pages: 243-254
  • NAID: 130004470668
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The short chain fatty acid receptor, GPR43, is expressed by enteroeodncrine cells and mucosal mast cells in the rat intestine. (2006)
  • Author(s): Karaki, S., Mitsui, R., Hayashi, H., Kato, I., Sugiya, H., Iwanaga, T., Furuness, J.B., Kuwahara, A.
  • Journal Title: Cell ＆ Tissue Research 324(3) Pages: 353-360
• [Journal Article] Fiber-free diet leads to impairment of neuronally mediated muscle contractile response in rat distal colon. (2006)
  • Author(s): Mitsui, R., Karaki, S.-I., Kubo, Y., Sugiura, Y., Kuwahara, A.
  • Journal Title: Neurogastroenterology ＆ Motility 18 Pages: 1093-1101
• [Journal Article] Cellular expression of monocarboxylate transporter(MCT) in the digestive tract of the mouse, rat, and human, with special reference to Slc5a8. (2006)
  • Author(s): Iwanaga, T., Takebe, K., Kato, I., karaki, S.-I., Kuwahara, A.
  • Journal Title: Biomedical Research 27(5) Pages: 243-254
  • NAID: 130004470668
• [Journal Article] A.2008. The tight junction component protein, claudin-4, is expressed by Enteric neurons in the rat distal colon
  • Author(s): Karaki, S.-I., Kaji, I., Otomo, Y., Tazoe, H., Kuwahara
  • Journal Title: Neuroscience Letters 428 Pages: 88-92
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine Cells and mucosal mast cells in the rat intestine
  • Author(s): karaki, S.-I., Mitsui, R., Hayashi, H., Kato, I., Sugiya, H., Iwanaga, T., Furness, J.B., Kuwahara, A
  • Journal Title: Cell & Tissue research 324 Pages: 353-360
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Neural reflex pathways in the contractile and secretory actions of short-chain fatty acids in the rat intestine (2007)
  • Author(s): Karaki, S.-I, Tazoe, H., Ono, S.and Kuwahara, A
  • Organizer: 5th Congress of the International Society for Autouomic Neuroscience
  • Place of Presentation: Kyoto,Japan
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Neural reflex pathways in the contractile and secretory actions of short Chain fatty acids in the rat intestine. (2007)
  • Author(s): karaki, S.-I., Tazoe, H., Ono, S. and Kuwahara, A
  • Organizer: 5th Congress of the International Society for Autonomic Nuroscience (ISAN2007)
  • Place of Presentation: Kyoto
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Neural reflex pathways in the contractile and secretory actions of short-chain fatty acids in the rat intestine (2007)
  • Author(s): Karaki, S. -I., Tazoe, H., Ono, S. and Kuwahara, A.
  • Organizer: 5th Congress of the International Society for Autonomic Neuroscience
  • Place of Presentation: Kyoto, Japan
• [Presentation] Role of prostaglandins for transepithelial ion transport in the guinea-pig distal colon. (2006)
  • Author(s): karaki, S.-I., Tazoe, H., Kuwahara, A
  • Organizer: The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
  • Place of Presentation: Central City/JM Marriott Hotel, Seoul Korea
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Effects of short-chain fatty acids on large intestinal motility and their mode of detection (2006)
  • Author(s): Karaki, S.-I., Mitsui, R., Ono, S., Tazoe, H., Yajima, T., Furness, J.B., Kuwahara, A
  • Organizer: 2006 Joint International Society Meeting in Neurogastroenterology and GI Motility
  • Place of Presentation: Seaport Hotel and World Trade Center Boston, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://physiology.u-shizuoka-ken.ac.jp
• [Remarks]
  • URL: http://physiology.u-shizuoka-ken.ac.jp