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Investigation of novel ANO1 inhibitor and its analgesic effects

Research Project

Project/Area Number 17K15793
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pain science
Research InstitutionShowa University (2019-2020)
Center for Novel Science Initatives, National Institutes of Natural Sciences (2018)
Okazaki Research Facilities, National Institutes of Natural Sciences (2017)

Principal Investigator

Takayama Yasunori  昭和大学, 医学部, 講師 (60711033)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsイオンチャネル / 疼痛 / 天然化合物 / 阻害剤 / 痛み / 鎮痛 / 抗炎症 / フラボノイド / 相互作用 / 鎮痛剤 / 天然資源 / 炎症性疼痛 / イオンチャネル相互作用 / TRPV1 / アノクタミン1 / TRPチャネル / アノクタミン / 掻痒 / イソプロピルシクロヘキサノール
Outline of Final Research Achievements

Anoctamin1 (ANO1) is a kind of chloride channel expressed in peripheral pain nerves, and the activation evokes pain sensation. I found that menthol inhibits ANO1 in my previous study. Therefore, I focused on novel findings of the mechanisms of ANO1 inhibition and pain reduction. In the results, I identified that 4-isopropylcyclohexanol, an analog of menthol, and liquiritigenin, a licorice-derived flavonoid, strongly inhibited ANO1. Furthermore, these chemicals reduced pain-related behavior in mice injected capsaicin into hind paw. These results indicate the novel strategy of pain control by natural compounds.

Academic Significance and Societal Importance of the Research Achievements

4ーイソプロピルシクエロヘキサノールは単純な構造をした化合物であるため、これをコアとして薬剤開発することによりイオンチャネルへの選択性や力価を調整できるため新たな創薬シーズとして期待される。また、甘草は多くの漢方薬や醤油に使用されており、東洋医学や食品の新たな機能性について今後言及することが可能となる。加えて、リクイリチゲニンと作用が似ているエストロゲンの効果も検討した結果、胎児発達に伴い産生されるエストリオールによってANO1は阻害された。その力価は乏しかったが、胎児と母親の新たな生理学的関係の解明に繋がるものと期待している。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (36 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (23 results) (of which Int'l Joint Research: 9 results,  Invited: 3 results) Book (1 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The Calcium-Activated Chloride Channel TMEM16A is Inhibitied by Liquiritigenin2021

    • Author(s)
      Kato Mami、Takayama Yasunori、Sunagawa Masataka
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 786511-786511

    • DOI

      10.3389/fphar.2021.628968

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1.2019

    • Author(s)
      Takayama Y, Derouiche S, Maruyama K, Tominaga M.
    • Journal Title

      Int J Mol Sci

      Volume: 20 Issue: 14 Pages: 3411-3411

    • DOI

      10.3390/ijms20143411

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] カルシウム活性化クロライドチャネルとカルシウム透過性チャネルの相互作用2019

    • Author(s)
      高山 靖規
    • Journal Title

      医学のあゆみ

      Volume: 270(10) Pages: 1017-1022

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception.2018

    • Author(s)
      Maruyama K, Takayama Y, Sugisawa E, Yamanoi Y, Yokawa T, Kondo T, Ishibashi KI, Sahoo BR, Takemura N, Mori Y, Kanemaru H, Kumagai Y, Martino MM, Yoshioka Y, Nishijo H, Tanaka H, Sasaki A, Ohno N, Iwakura Y, Moriyama Y, Nomura M, Akira S, Tominaga M.
    • Journal Title

      iScience

      Volume: 6 Pages: 306-318

    • DOI

      10.1016/j.isci.2018.08.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physiological responses of ionotropic histamine receptors, PxHCLA and PxHCLB, to neurotransmitter candidates in a butterfly, Papilio xuthus2018

    • Author(s)
      Akashi Hiroshi D.、Chen Pei-Ju、Akiyama Tokiho、Terai Yohey、Wakakuwa Motohiro、Takayama Yasunori、Tominaga Makoto、Arikawa Kentaro
    • Journal Title

      The Journal of Experimental Biology

      Volume: 221 Pages: 2234-2242

    • DOI

      10.1242/jeb.183129

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation2018

    • Author(s)
      Tsuchiya Masaki、Hara Yuji、Okuda Masaki、Itoh Karin、Nishioka Ryotaro、Shiomi Akifumi、Nagao Kohjiro、Mori Masayuki、Mori Yasuo、Ikenouchi Junichi、Suzuki Ryo、Tanaka Motomu、Ohwada Tomohiko、Aoki Junken、Kanagawa Motoi、Toda Tatsushi、Nagata Yosuke、Matsuda Ryoichi、Takayama Yasunori、Tominaga Makoto、Umeda Masato
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2049-2049

    • DOI

      10.1038/s41467-018-04436-w

    • NAID

      120006471161

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physiological significances of TRP-ANO1 interaction2018

    • Author(s)
      Takayama Y, Shibasaki K, Furue H, Uta D, Tominaga M
    • Journal Title

      PAIN RESEARCH

      Volume: 33 Pages: 1-9

    • NAID

      130007378640

    • Related Report
      2017 Research-status Report
  • [Presentation] 甘草由来フラボノイドとエストロゲンによるTMEM16A阻害2021

    • Author(s)
      加藤真未, 高山靖規, 砂川正隆
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 環境因子に影響されるイオンチャネルの機能解析2021

    • Author(s)
      高山靖規
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The effect of an acupuncture "press tack needle" treatment on orexin secretion under acute stress2020

    • Author(s)
      Fujiwara A, Tsukada M, Iduno T, Ikemoto H, Takayama Y, Guo S, Liu Y, Hisamitsu T, Sunagawa M
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Contribution of oxytocin to the anti-stress effect of the Kampo medicine Kamikihito -Part II-2020

    • Author(s)
      Tsukada M, Ikemoto H, Adachi N, Takayama Y, Okumo T, Yogi W, Kato M, Hisamitsu T, Sunagawa M
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ANO1 inhibition by the extracts from Glechoma Hederacea2020

    • Author(s)
      Takayama Y, Kato M, Tsukada M, Adachi N, Ikemoto H, Sunagawa M
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of kampo medicine containing ginger on TRPV1-ANO1 interaction2020

    • Author(s)
      Kato M, Takayama Y, Tsukada M, Sunagawa M
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Preemptive analgesia provided by complementary approaches in acute inflammatory pain model rats2020

    • Author(s)
      Ebihara N, Ikemoto H, Adachi N, Ebihara T, Ebihara K, Oike J, Kunieda Y, Takayama Y, Hisamitsu T, Sunagawa M
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Possible Mechanisms of Astrocyte Senescence in a Hepatic Encephalopathy Model2020

    • Author(s)
      Adachi N, Ando M, Sakhri F, Ikemoto H, Ohasi Y, Tsukada M, Takayama Y, Hirai Y, Sunagawa M
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] TRPV1-ANO1相互作用の炎症性疼痛への関与2019

    • Author(s)
      高山靖規, 富永真琴
    • Organizer
      第41回日本疼痛学会
    • Related Report
      2019 Research-status Report
  • [Presentation] TRPV4 is functionally expressed in cultured mouse Schwann cells2019

    • Author(s)
      Xiaona Feng, Yasunori Takayama, Makoto Tominaga
    • Organizer
      FAOPS 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional interaction between TRPM8 and ANO12019

    • Author(s)
      Mingyi Dong, Hong Dung Thi Nguyen, Yasunori Takayama, Makoto Tominaga
    • Organizer
      FAOPS 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of TRPV3-ANO1 interaction in keratinocyte wound healing2019

    • Author(s)
      Yu Yamanoi, Yasunori Takayama, Makoto Tominaga
    • Organizer
      FAOPS 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of amino acids involved in the 4-isopropylcyclohexanol actioin on TRP channels2019

    • Author(s)
      Hong Dung Thi Nguyen, Yasunori Takayama, Makoto Tominaga
    • Organizer
      FAOPS 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] TRPV1 and ANO1/TMEM16A interaction in inflammatory pain conditions2019

    • Author(s)
      Yasunori Takayama, Makoto Tominaga
    • Organizer
      FAOPS 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 炎症におけるTRPV1-ANO1相互作用の役割2018

    • Author(s)
      高山靖規, 富永真琴
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pain enhancing mechanism through TRPV1-ANO1 interaction and its pharmacological control2018

    • Author(s)
      Yasunori Takayama
    • Organizer
      Sophion - International Symposium on channelopathy and drug discovery
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Interaction between TRPV1 and ANO1/TMEM16A in acute and inflammatory pain conditions2018

    • Author(s)
      Yasunori Takayama, Makoto Tominaga
    • Organizer
      IASP 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pain and itch reductions by 4-isopropylcyclohexanol targeting TRP channels and ANO12018

    • Author(s)
      Takayama Y, Furue H, Tominaga M
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Pathophysiological significance of TRPV1-ANO1 interaction in inflammation2018

    • Author(s)
      Takayama Y, Tomianga M
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Comprehensive regulation of ion dynamics through TRP-ANO1 interaction in primary sensory neurons2017

    • Author(s)
      Takayama Y,
    • Organizer
      The 7th Asian Pain Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Inhibitory effects of 4-isopropylcyclohexanol on ion channels2017

    • Author(s)
      Takayama Y, Furue H, Tominaga M
    • Organizer
      第39回日本疼痛学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Analgesia via comprehensive inhibition of ion channels by 4-isopropylcyclohexanol2017

    • Author(s)
      Takayama Y, Furue H, Tominaga M
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Pharmacological effects of 4-isopropylcyclohexanol on TRP channel and ANO1/TMEM16A2017

    • Author(s)
      Takayama Y, Furue H, Tominaga M
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] Advances in Pain Research: Mechanisms and Modulation of Chronic Pain2018

    • Author(s)
      Yasunori Takayama
    • Total Pages
      265
    • Publisher
      Springer
    • Related Report
      2018 Research-status Report
  • [Remarks] 妊娠期に分泌されるエストロゲンに類似するフラボノイドによる新たなイオンチャネル阻害を発見

    • URL

      https://www.showa-u.ac.jp/news/nid00002946.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 昭和大学 医学部 生体制御学部門

    • URL

      https://www.showa-u.ac.jp/education/med/major/physio-1.html

    • Related Report
      2019 Research-status Report
  • [Remarks] カンジダ感染症における不快情動を惹起する分子メカニズムの解明

    • URL

      https://www.nips.ac.jp/release/2018/09/post_376.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 新たな鎮痛薬創薬シーズの発見

    • URL

      http://www.nips.ac.jp/nips_research/2018/02/_4-.html

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 活性抑制剤および皮膚感覚過敏抑制剤2017

    • Inventor(s)
      高山靖規、富永真琴
    • Industrial Property Rights Holder
      大学共同利用機関法人自然科学研究機構
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-158822
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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