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Analysis of drug absorption behavior in the enteric nervous system-related gastrointestinal diseases

Research Project

Project/Area Number 23590181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionOkayama University

Principal Investigator

HIGAKI Kazutaka  岡山大学, 医歯(薬)学総合研究科, 教授 (60284080)

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)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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 / Mrp2 / Western blot / 発現タンパク / 有機アニオン系薬物 / Ussing type chamber / 消化器疾患 / Caco-2
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.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (6 results)

All 2014 2012 2011 Other

All Presentation (5 results) Remarks (1 results)

  • [Presentation] セロトニン症候群発症時における薬物の経口吸収挙動に関する基礎的検討2014

    • Author(s)
      坡山幸恵、中島 駿、大河原 賢一、檜垣 和孝
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      ソニックシティ(さいたま市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] セロトニン症候群発症時における薬物の経口吸収挙動に関する基礎的研究2012

    • Author(s)
      中島駿、岩本武晴、高梨雅史、大河原賢一、木村聰城郎、檜垣和孝
    • Organizer
      日本薬剤学会第27年会
    • Place of Presentation
      神戸国際会議場,神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] セロトニン症候群発症時における薬物の経口吸収挙動に関する基礎的研究2012

    • Author(s)
      中島 駿
    • Organizer
      日本薬剤学会第27年会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 有機アニオン性化合物の経口吸収挙動に及ぼすセロトニン枯渇の影響2011

    • Author(s)
      三木朋子、橋本賢太、大河原賢一、木村聰城郎、檜垣和孝
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      タワーホール船堀,東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 有機アニオン性化合物の経口吸収挙動に及ぼすセロトニン枯渇の影響2011

    • Author(s)
      三木 朋子、橋本 賢太、大河原 賢一、木村 聰城郎、檜垣 和孝
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      タワーホール船堀, 東京
    • Related Report
      2011 Research-status Report
  • [Remarks] ホームページ

    • URL

      http://www.pharm.okayama-u.ac.jp/department/

    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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