A new treatment strategy for diarrhea and constipation via intestinal aquaporin

• Project/Area Number: 25860195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Hoshi University
• Principal Investigator: IKARASHI NOBUTOMO 星薬科大学, 薬学部, 助教 (40409363)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: アクアポリン / 下痢 / 便秘 / モルヒネ / センノシドA / 大腸 / 瀉下剤 / 止瀉剤

Outline of Final Research Achievements

Aquaporin (AQP), which are water channels, plays an important role in the water transport in the body. In this study, we investigated the role of colon AQP3 in the development of diarrhea and constipation. It was clarified that sennoside A induced the diarrhea accompanied by the decrease of the colon AQP3. In addition, it was revealed that morphine induced the constipation accompanied by the increase of the colon AQP3. Therefore, new laxatives and antidiarrheals targeting intestinal AQP3 may be developed in the future.

Research Products

• [Journal Article] Morphine-induced constipation develops with increased aquaporin-3 expression in the colon via increased serotonin secretion (2015)
  • Author(s): R. Kon, N. Ikarashi, A. Hayakawa, Y. Haga, A. Fueki, Y. Kusunoki, M. Tajima, W. Ochiai, Y. Machida, K. Sugiyama
  • Journal Title: Toxicol. Sci. Volume: 印刷中 Issue: 2 Pages: 337-347
  • DOI: 10.1093/toxsci/kfv055
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract (2014)
  • Author(s): Kon Risako; Ikarashi Nobutomo; Nagoya Chika; Takayama Tomoko; Kusunoki Yoshiki; Ishii Makoto; Ueda Harumi; Ochiai Wataru; Machida Yoshiaki; Sugita Kazuyuki; Sugiyama Kiyoshi
  • Journal Title: Journal of ethnopharmacology Volume: 152 Issue: 1 Pages: 190-200
  • DOI: 10.1016/j.jep.2013.12.055
  • Peer Reviewed / Open Access
• [Journal Article] Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract (2014)
  • Author(s): R. Kon, N. Ikarashi, C. Nagoya, T. Takayama, Y. Kusunoki, M. Ishii, H. Ueda, W. Ochiai, Y. Machida, Y. Sugita, and K. Sugiyama
  • Journal Title: J. Ethnopharmacol. Volume: 152 Pages: 190-200
  • Peer Reviewed
• [Journal Article] Hepatic early inflammation induces downregulation of hepatic cytochrome P450 expression and metabolic activity in the dextran sulfate sodium-induced murine colitis (2014)
  • Author(s): Y. Kusunoki, N. Ikarashi, Y. Hayakawa, M. Ishii, R. Kon, W. Ochiai, Y. Machida, and K. Sugiyama
  • Journal Title: Eur. J. Pharm. Sci. Volume: 54 Pages: 17-27
  • Peer Reviewed
• [Presentation] モルヒネによる便秘は、セロトニンの分泌亢進を介した大腸AQP3の発現増加により発症する (2015)
  • Author(s): 五十嵐信智 ほか
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] センノシドAの新規瀉下作用メカニズムの解明とその適正使用に関する研究 (2014)
  • Author(s): 五十嵐信智 ほか
  • Organizer: 第8回日本緩和医療薬学会年会
  • Place of Presentation: 愛媛
  • Year and Date: 2014-10-03 – 2014-10-05
• [Presentation] 水チャネル『アクアポリン』を介した大黄の新規瀉下作用メカニズムの解明とその成分研究 (2014)
  • Author(s): 五十嵐信智
  • Organizer: 第31回和漢医薬学会学術大会
  • Place of Presentation: 千葉
  • Year and Date: 2014-08-30 – 2014-08-31
  • Invited
• [Presentation] 大黄の瀉下作用における大腸アクアポリン3の役割 (2014)
  • Author(s): 今理紗子, 五十嵐信智, 名古屋智香, 落合 和, 杉山 清
  • Organizer: 第10回日本消化管学会総会学術集会
  • Place of Presentation: 福島
• [Presentation] 大黄は大腸アクアポリン3の発現低下を介して瀉下作用を発揮する (2013)
  • Author(s): 今理紗子, 五十嵐信智, 名古屋智香, 楠 欣己, 落合 和, 杉山 清
  • Organizer: 第64回日本東洋医学会学術総会
  • Place of Presentation: 鹿児島
• [Presentation] 大黄およびその主成分センノシドAは大腸アクアポリン3の発現低下を介して瀉下作用を発揮する (2013)
  • Author(s): 五十嵐信智, 今理紗子, 名古屋智香, 落合 和, 杉山 清
  • Organizer: 第30回和漢医薬学会学術大会
  • Place of Presentation: 金沢
• [Presentation] Effects of morphine and its metabolites on the expression of AQP3 in the colon (2013)
  • Author(s): Risako Kon, Nobutomo Ikarashi, Ayako Mimura, Tomohiko Iizasa, Kiyomi Suenaga, Noriko Suzuki, Reiko Hiruma, Yoshiki Kusunoki, Makoto Ishii, Wataru Ochiai, and Kiyoshi Sugiyama
  • Organizer: 10th International ISSX Meeting
  • Place of Presentation: Toronto