Role of TRP channels in the human heat loss responses

• Project/Area Number: 20H04065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: University of Tsukuba
• Principal Investigator: Fujii Naoto 筑波大学, 体育系, 助教 (00796451)
• Co-Investigator(Kenkyū-buntansha): 天野 達郎 新潟大学, 人文社会科学系, 准教授 (60734522) ; 近藤 徳彦 神戸大学, 人間発達環境学研究科, 教授 (70215458) ; 西保 岳 筑波大学, 体育系, 教授 (90237751)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2022: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2021: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: マイクロダイアリシス / 熱中症 / 暑熱 / イオンチャネル / 皮内透析法 / TRPチャネル / TRPV1 / TRPM8 / 熱放散 / 発汗 / 運動 / TRP / 体温 / 地球温暖化

Outline of Research at the Start

透析は、特に腎機能が低下した患者において、体内の老廃物を除去する目的で用いられる。本研究では、この透析のプローブを皮膚表層に埋め込み、半透膜を介して薬物を皮膚に投与し、TRPチャネルの活動を亢進、あるいは抑制することでメカニズムの解明を目指す。実験①では、TRPチャネル阻害薬の選定と濃度決定を行う。実験②では、TRPチャネルが暑熱下運動時の熱放散反応に及ぼす影響を明らかにする。実験③では、TRPチャネルが暑熱順化による熱放散反応向上に及ぼす影響を明らかにする。

Outline of Final Research Achievements

The peripheral mechanisms that regulate heat dissipation (sweating and skin vasodilation) in humans are still unknown. In the present study the principal investigater examined how TRP channels contribute to the peripheral heat dissipation responses in humans. The present study revealed that activation of TRPA1 channels mediate cutaneous vasodilation. Future studies are warranted to clarify whether this channel contributes to the heatloss response of cutaneous vasodilation. If TRPA1 channels contribute to the heatloss response of cutaneous vasodilation, new heat countermeasures utilizing cinnamon (cinnamaldehyde) and horseradish (isothiocyanate), which activate this channel, would be developed.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られたデータは、熱中症を防ぐ具体的方策を構築する上で極めて重要な知見となる。実際の活用例としては、同定された受容体やイオンチャネルを選択的に活性化し、運動時の熱放散反応を向上させるサプリメント・処方箋・食事法の開発が挙げられる。これらの新しい熱中症予防方法の確立・普及により、暑熱下での学校体育やスポーツ活動の現場での熱中症の発生件数を大幅に低下させることができると期待される。

Research Products

• [Int'l Joint Research] University of Ottawa(カナダ)
• [Int'l Joint Research] Massey University(ニュージーランド)
• [Int'l Joint Research] University of Ottawa(カナダ)
• [Int'l Joint Research] Massey University(ニュージーランド)
• [Int'l Joint Research] Hubei Normal University(中国)
• [Journal Article] Involvement of nitric oxide synthase and reactive oxygen species in TRPA1-mediated cutaneous vasodilation in young and older adults (2023)
  • Author(s): McGarr Gregory W.、King Kelli E.、Cassan Casey J.M.、Janetos Kristina-Marie T.、Fujii Naoto、Kenny Glen P.
  • Journal Title: Microvascular Research Volume: 145 Pages: 104443-104443
  • DOI: 10.1016/j.mvr.2022.104443
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TMEM16A blockers T16Ainh‐A01 and benzbromarone do not modulate the regulation of sweating and cutaneous vasodilatation in humans in vivo (2022)
  • Author(s): Fujii Naoto、Amano Tatsuro、Kenny Glen P.、M?ndel Toby、Lei Tze‐Huan、Honda Yasushi、Kondo Narihiko、Nishiyasu Takeshi
  • Journal Title: Experimental Physiology Volume: 107 Issue: 8 Pages: 844-853
  • DOI: 10.1113/ep090521
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TRPA1 Channel Activation With Cinnamaldehyde Induces Cutaneous Vasodilation Through NOS, but Not COX and KCa Channel, Mechanisms in Humans (2022)
  • Author(s): Kataoka Yufuko、Kenny Glen P.、Nishiyasu Takeshi、Amano Tatsuro、M?ndel Toby、Zheng Huixin、Lei Tze-Huan、Watanabe Koichi、Fujii Naoto
  • Journal Title: Journal of Cardiovascular Pharmacology Volume: 79 Issue: 3 Pages: 375-382
  • DOI: 10.1097/fjc.0000000000001188
  • Peer Reviewed / Int'l Joint Research
• [Presentation] TRPA1 channel activation with cinnamaldehyde induces cutaneous vasodilation through NOS, but not COX and KCa channel, mechanisms in human (2021)
  • Author(s): Yufuko Kataoka, Glen Kenny, Takeshi Nishiyasu, Tatsuro Amano, Toby Mündel, Huixin Zheng, Tze-Huan Lei, Koichi Watanabe, Naoto Fujii
  • Organizer: Experimental Biology 2021
  • Int'l Joint Research