2007 Fiscal Year Final Research Report Summary
Regulation of ion transpot by short chain fatty acids receptor, GPR43 in colonic epithelia
| Project/Area Number |
18590207
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | University of Shizuoka |
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Principal Investigator |
KUWAHARA Atsukazu University of Shizuoka, Institute for Environmental Sciences, professor (60142890)
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| Co-Investigator(Kenkyū-buntansha) |
KARAKI Shin-ichirou University of Shizuoka, Institute for Environmental Sciences, professor (00363903)
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| Project Period (FY) |
2006 – 2007
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| Keywords | short chain fatty acid / G protein coupled receptor / colonic function / inn transnnrt / dietary fiber / intestinal motility / chemosensory / epithelium |
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| 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.
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Research Products
(16 results)
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[Journal Article] Expression of the short-chain fatty acid receptol,GPR43,in human colon2008
Author(s)
Karaki, S.-I., Tazoe, H., Hayashi, H.Kashiwabara, H., Tooyama, K., Suzuki, Y.and Kuwahara, A
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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
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[Journal Article] Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglaindins,sensory afferent neuropeptides and nitric oxides2008
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
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Journal Title
Regulatory peptides Available online 20,Feb
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Expression of the short-chain fatty acid receptor, GPR43, in human Colon2008
Author(s)
Karaki, S.-I., Tazoe, H., Hayashi, H., Kashiwabara, H., Tooyama, K., Suzuki, Y. and Kuwahara, A
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Journal Title
Journal of Molecular Histology 38
Pages: 135-142
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The tight junction component protein,claudin-4,is expressed by enteric neurons in the rat distal colon2007
Author(s)
Kairki, S.-I., Kaji, I., Otomo, Y., Tazoe, H.and Kuwahara, A
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Journal Title
Neuroscience Letters 428
Pages: 88-92
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a82006
Author(s)
Iwanaga, T., Takebe, K., Kato, I., Karaki, S., Kuwahara, A
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Journal Title
Biomedical Research 27
Pages: 243-254
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Neuroscience Letters 428
Pages: 88-92
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Cell & Tissue research 324
Pages: 353-360
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of short-chain fatty acids on large intestinal motility and their mode of detection2006
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
Year and Date
20060914-17
Description
「研究成果報告書概要(欧文)」より
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