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Intravesical Kv7 channel opener using new drug delivery system

Research Project

Project/Area Number 19K09710
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionTottori University

Principal Investigator

Honda Masashi  鳥取大学, 医学部, 准教授 (20362890)

Co-Investigator(Kenkyū-buntansha) 武中 篤  鳥取大学, 医学部, 教授 (50368669)
引田 克弥  鳥取大学, 医学部附属病院, 特命准教授 (50403407)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords下部尿路機能 / 膀胱内圧測定 / 受容体 / 神経ペプチド / カリウムチャネル開口薬 / 排尿機能 / 薬理学 / 生理学 / ドラッグデリバリーシステム / 膀胱内注入
Outline of Research at the Start

本研究では、従来の薬物療法では改善できない過活動膀胱の症状(頻尿、尿意切迫感など)に対する新しい薬剤の膀胱内注入療法を確立するために、実験動物を用いた基礎研究を行う。
使用する薬剤はKv7チャネル開口薬で、膀胱に尿をためやすくする作用があることは分かってきているが、その作用機序は十分には解明されていない。また膀胱内に注入した場合の効果も不明な点が多い。
膀胱内に注入する薬剤の膀胱組織への吸収効率を改善するため、注入前に薬剤を特殊処理し実験を行う予定である。

Outline of Final Research Achievements

In a series of studies investigating the role of voltage-gated potassium 7 (Kv7) channel openers on lower urinary tract function, we investigated the effects of intravenous administration of ghrelin on the micturition reflex in rats.
Continuous cystometrograms were performed under urethane anesthesia. Ghrelin was administered intravenously to evaluate changes in bladder activity. Intravenous administration of ghrelin increased intercontraction interval. These inhibitory effects of ghrelin were antagonized by intravenous naloxone administration. These results show that ghrelin inhibits the micturition reflex through an opioid-dependent mechanism in rats.

Academic Significance and Societal Importance of the Research Achievements

本研究課題の成果から、未だにその作用が十分に解明されていないghrelinが正常排尿反射に果たす役割が解明された。神経ペプチドghrelinの経静脈投与は、ラット正常排尿反射をopioidメカニズムを介して抑制する可能性が示唆された。
Ghrelinの経静脈投与による下部尿路機能以外の全身への作用は十分には判明していないものの、本研究成果は過活動膀胱などの下部尿路機能障害に対する新しい薬物療法を確立していく上で、重要な基盤になる知見であると考えている。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Effects of intravesical administration of sensory neuron-specific receptor agonist on voiding function in rats with cyclophosphamide-induced cystitis.2019

    • Author(s)
      Honda M, Tsounapi P, Teraoka S, Kimura Y, Hikita K, Takenaka A
    • Journal Title

      Cent European J Urol

      Volume: 72 Pages: 142-148

    • DOI

      10.5173/ceju.2019.1949

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Activation of group I and III metabotropic glutamate receptors influences the micturition reflex in urethane-anesthetized rats2020

    • Author(s)
      Honda M, Shimizu R, Teraoka S, Nishikawa R, Kimura Y, Tsounapi P, Iwamoto H, Morizane S, Hikita K, Takenaka A
    • Organizer
      American Urological Association Annual Meeting 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inhibitory effect of ghrelin on micturition reflex in uretahne-anesthetized rats2020

    • Author(s)
      Honda M, Shimizu R, Teraoka S, Nishikawa R, Kimura Y, Tsounapi P, Iwamoto H, Morizane S, Hikita K, Takenaka A
    • Organizer
      35th Annual European Urological Association Congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Supraspinal and spinal effects of group I and III metabotropic glutamate receptor agonists on the micturition reflex in rats2020

    • Author(s)
      Honda M, Teraoka S, Kimura Y, Panagiota T, Shimizu S, Shimizu T, Morizane S, Hikita K, Saito M, Takenaka A
    • Organizer
      International Continence Society Annual Meeting 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ghrelin-mediated regulation of the micturition reflex in urethane anesthetized rats2019

    • Author(s)
      Honda M, Kimura Y, Tsounapi P, Hikita K, Saito M, Takenaka A
    • Organizer
      American Urological Association Annual Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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