2013 Fiscal Year Final Research Report
Analysis of drug absorption behavior in the enteric nervous system-related gastrointestinal diseases
| Project/Area Number |
23590181
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
HIGAKI Kazutaka 岡山大学, 医歯(薬)学総合研究科, 教授 (60284080)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Toshikirou 岡山大学, 大学院医歯薬学総合研究科, 特命教授 (10025710)
OOGAWARA Kenichi 岡山大学, 大学院医歯薬学総合研究科, 准教授 (30291470)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 腸神経系 / セロトニン / 有機アニオン系化合物 / 分泌 / Caco-2細胞 / ラット単離小腸粘膜 / MRP2 / BCRP |
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| Research Abstract |
Serotonin (5-HT) is related to the regulation of gastrointestinal (GI) function as a neurotransmitter in enteric nervous system (ENS) and GI hormone, and the disorder of 5-HT metabolism is suggested to associate with several GI diseases such as irritable bowel syndrome. In this project, we evaluated the effect of 5-HT depletion on the secretion of organic anions into the small intestinal lumen, influencing their absorption behavior. Phenol red (PR), a model compound, was clarified to be predominantly transported from basal to apical sides in Caco-2 cells and rat small intestine. Furthermore, it was indicated that MRP2 and BCRP contributed to the secretory transport of PR and that the secretory transport of PR was significantly enhanced in 5-HT-depleted rats, which was responsible for the enhancement of MRP2 and BCRP functions, based on their enhanced expression in the brush border membrane of small intestinal epithelial cells of 5-HT-depleted rats.
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