Molecular mechanism of luminal pressure reception and ATP release in gastrointestinal epithelium

2017 Fiscal Year Final Research Report

• Project/Area Number: 26870214
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology; Gastroenterology
• Research Institution: University of Toyama
• Principal Investigator: Mihara Hiroshi 富山大学, 大学院医学薬学研究部(医学), 助教 (00612623)
• Co-Investigator(Renkei-kenkyūsha): NISHIZONO Hirofumi 富山大学, 研究推進機構 研究推進総合支援センター, 助教 (10502289) ; SUGIYAMA Toshiro 富山大学, 大学院医学薬学研究部(医学), 教授 (00196768) ; TOMINAGA Makoto 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 教授 (90260041) ; TABUCHI Yoshiaki 富山大学, 研究推進機構 研究推進総合支援センター, 教授 (20322109) ; WATANABE Shiro 富山大学, 和漢医薬学総合研究所, 准教授 (00222406) ; UCHIDA Kunitoshi 福岡歯科大学, 歯学部, 講師 (20581135) ; KOIZUMI Schuichi 山梨大学, 総合研究部, 教授 (10280752)
• Research Collaborator: Boudaka Ammar ; YAMAWAKI Hidemoto ; SUZUKI Nobuhiro ; Muhammad Jibran Sualeh ; KOZAWA Toyomi ; Fujinami Haruka ; ANDO Takayuki ; NANJO Sohachi
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 消化管上皮 / 伸展刺激 / ATP放出 / TRPV4 / VNUT

Outline of Final Research Achievements

Approximately 15% of Japanese people have chronic abdominal pain of unknown origin and hypersensitivity to gastrointestinal pressure is one of possible causes. The esophagus senses a tension with mechano-sensitive TRPV4 ion channel and releases bag-like adenosine triphosphate (ATP) using its transporter (VNUT). As a result of the study, TRPV4 and VNUT are present not only in the esophagus but also from the stomach to the rectum, and ATP is released via VNUT by TRPV4 stimulation, including stretch stimuli. Mice lacking TRPV4 have gastric motor abnormality and Helicobacter pylori infection decreases TRPV4 (gene methylation). It has also succeeded in quantifying the TRPV4 stimulating component synthesized in the gastrointestinal tract and so the possibility of quantifying invisible abdominal pain has come out.

Free Research Field

消化器内科