| Budget Amount *help |
¥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)
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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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