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Strategy targeting neuropeptide receptors in the central and peripheral nervous systems in treatment of underactive bladder

Research Project

Project/Area Number 22591787
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionUniversity of Yamanashi

Principal Investigator

YOSHIYAMA Mitsuharu  山梨大学, 大学院・医学工学総合研究部, 教授 (20422694)

Co-Investigator(Kenkyū-buntansha) NAKAGOMI Hiroshi  山梨大学, 医学部附属病院, 助教 (80418714)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords排尿障害 / 膀胱 / 尿道 / 糖尿病 / 脳下垂体アデニル酸シクラーゼ活性化ポリペプチド(PACAP) / マウス / 低活動膀胱 / 下部尿路障害 / 脊髄 / 神経ペプチド / 膀胱コンプライアンス / 排尿収縮圧 / 残尿 / 反射排尿 / 尿意切迫感 / 切迫性尿失禁 / 神経障害 / 下部尿路機能 / 外尿道括約筋 / 脊髄損傷 / 末梢神経障害
Research Abstract

Lower urinary tract function of genetically mutated mice with diabetes mellitus (DM) was evaluated and compared to that of the wild-type mice. The results suggest that in DM mice, mechanism controlling voiding in the forebrain is devoid of appropriate inhibitory function, and thus the animals present reflex micturition. DM mice at age of 30 week-old still retain voiding efficiency more than 80%, albeit moderately present underactive bladder. Intrathecal administration of PACAP-38 increased maximal voiding pressure and partially suppressed external urethral sphincter activity, suggesting the possibility that stimulation of spinal PACAP receptors enhancesbladder contractility and ameliorates efficiency for voiding.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (55 results)

All 2013 2012 2011 2010 Other

All Journal Article (23 results) (of which Peer Reviewed: 10 results) Presentation (32 results)

  • [Journal Article] 医薬ジャーナル2013

    • Author(s)
      武田正之、荒木勇雄、澤田智史、中込宙史、望月勉、小林英樹、座光寺秀典、芳山充晴
    • Journal Title

      新薬展望2013

      Volume: Vol.49 S-1

    • Related Report
      2012 Final Research Report
  • [Journal Article] Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats.2013

    • Author(s)
      Yoshiyama M, Roppolo JR, Takeda M, de Groat WC
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 304

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats2013

    • Author(s)
      Mitsuharu Yoshiyama
    • Journal Title

      American Journal of Physiology - Renal Physiology

      Volume: 304 Issue: 4 Pages: F390-F396

    • DOI

      10.1152/ajprenal.00574.2012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 排尿障害治療薬2013

    • Author(s)
      武田正之
    • Journal Title

      医薬ジャーナル 新薬展望

      Volume: 49 (S-1) Pages: 308-319

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 排尿障害におけるβ3受容体刺激(作動)薬2012

    • Author(s)
      武田正之、中込宙史、芳山充晴、荒木勇雄
    • Journal Title

      診断と治療

      Volume: 第100巻・第8号 Pages: 1379-1385

    • Related Report
      2012 Final Research Report
  • [Journal Article] 排尿障害におけるβ3受容体作動薬2012

    • Author(s)
      武田正之、中込宙史、芳山充晴、荒木勇雄
    • Journal Title

      Progress in Medicine

      Volume: Vol.32 (No.4) Pages: 37-42

    • Related Report
      2012 Final Research Report
  • [Journal Article] 排尿障害におけるβ3受容体刺激(作動)薬2012

    • Author(s)
      武田正之
    • Journal Title

      診断と治療

      Volume: 100 Pages: 1379-1385

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 排尿障害におけるβ3受容体作動薬2012

    • Author(s)
      武田正之
    • Journal Title

      Progress in Medicine

      Volume: 32 Pages: 37-42

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 第4回国際尿失禁会議からの報告 Committee3 Cell Biology 「細胞生物学」2011

    • Author(s)
      武田正之、中込宙史、宮本達也、吉良聡、芳山充晴
    • Journal Title

      排尿障害プラクティス

      Volume: Vol.19(1) Pages: 66-88

    • Related Report
      2012 Final Research Report
  • [Journal Article] Bladder outlet obstruction induced expression of prostaglandin E2receptor subtype EP4 in the rat bladder: a possible counteractive mechanism against detrusor overactivity2011

    • Author(s)
      Beppu M, Araki I, Yoshiyama M, Du S, Kobayashi H, Zakoji H, Takeda M.
    • Journal Title

      J Urol

      Volume: 186 Pages: 2463-2469

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bladder outlet obstruction induced expression of prostaglandin E2receptor subtype EP4 in the rat urinary bladder: a possible counteractive mechanism against detrusor overactivity2011

    • Author(s)
      Beppu M, Araki I, Yoshiyama M, Du S, Kobayashi H, Zakoji H, Takeda M
    • Journal Title

      J Urol

      Volume: 186(6) Issue: 6 Pages: 2463-2469

    • DOI

      10.1016/j.juro.2011.07.087

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 第4回国際尿失禁会議からの報告Committee3 Cell Biology「細胞生物学」2011

    • Author(s)
      武田正之, 他
    • Journal Title

      排尿障害プラクティス

      Volume: Vol.19 Pages: 66-88

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 第4回国際尿失禁会議からの報告Committee 3 Cell Biology「細胞生物学」.2011

    • Author(s)
      武田正之, 等
    • Journal Title

      排尿障害プラクティス

      Volume: 19(1) Pages: 66-88

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 尿路上皮と排尿2010

    • Author(s)
      荒木勇雄、中込宙史、望月勉、小林英樹、芳山充晴、武田正之
    • Journal Title

      臨床検査

      Volume: Vol.54(7) Pages: 726-730

    • Related Report
      2012 Final Research Report
  • [Journal Article] 排尿障害の基礎2010

    • Author(s)
      芳山充晴
    • Journal Title

      臨床検査

      Volume: Vol.54(7) Pages: 717-725

    • Related Report
      2012 Final Research Report
  • [Journal Article] Sensor mechanism and afferent signal transduction of the urinary bladder: special focus on transient receptor potential ion channels2010

    • Author(s)
      Takeda M, Mochizuki T, Yoshiyama M, Nakagomi H, Kobayashi H, Sawada N, Zakohji H, Du S, Araki I
    • Journal Title

      LUTS (Lower Urinary Tract Symptoms)

      Volume: 2 Pages: 51-60

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Emerging families of ion channels involved2010

    • Author(s)
      Araki I,Yoshiyama M,Kobayashi H,Mochizuki T,Du S,Okada Y,Takeda M.
    • Journal Title

      urinary bladder nociception Pharmaceuticals

      Volume: 3 Pages: 2248-2267

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid: in vivo evaluations of the sex difference in decerebrate unanesthetized mice2010

    • Author(s)
      Yoshiyama M, Araki I, Kobayashi H, Zakoji H, Takeda M.
    • Journal Title

      Am.J.Physiol.Renal.Physiol

      Volume: 298

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid: in vivo evaluations of the sex difference in decerebrate unanesthetized mice.2010

    • Author(s)
      Yoshiyama M, et al.
    • Journal Title

      American Journal of Physiology-Renal Physiology

      Volume: 298 Pages: 1351-1359

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging families of ion channels involved in urinary bladder nociception.2010

    • Author(s)
      Araki I, et al.
    • Journal Title

      Pharmaceuticals

      Volume: 3 Pages: 2248-2267

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensor mechanism and afferent signal transduction of the urinary bladder: special focus on transient receptor potential ion channels.2010

    • Author(s)
      Takeda M, et al.
    • Journal Title

      LUTS(Lower Urinary Tract Symptoms)

      Volume: 2 Pages: 51-60

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 排尿障害の基礎.2010

    • Author(s)
      芳山充晴
    • Journal Title

      臨床検査

      Volume: 54(7) Pages: 717-725

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 尿路上皮と排尿.2010

    • Author(s)
      荒木勇雄, 等
    • Journal Title

      臨床検査

      Volume: 54(7) Pages: 726-730

    • Related Report
      2010 Annual Research Report
  • [Presentation] Blockade of neural transmission via metabotropic glutamate receptor subtype 5 facilitates urine storage without impairing bladder contractility and micturition in mice(Abstract No. 133)2012

    • Author(s)
      Yoshiyama M, Tsuchiya S, Takeda M.
    • Organizer
      International Continence Society 42ndAnnual meeting, China National Convention Centre
    • Place of Presentation
      Beijing, China
    • Related Report
      2012 Final Research Report
  • [Presentation] Vesicular nucleotide transporter (VNUT) is a key molecule for mechanosensing in the human urinary bladder: negative correlation between VNUT expression in human bladder mucosa and first desire to void. (Abstract No. 12)2012

    • Author(s)
      Nakagomi H, Mochizuki T, Miyamoto T, Kira S, Yoshiyama M, Kawahara K, Moriyama Y, Koizumi S, Takeda M.
    • Organizer
      International Continence Society 42nd Annual meeting, China National Convention Centre
    • Place of Presentation
      Beijing, China
    • Related Report
      2012 Final Research Report
  • [Presentation] 代謝型グルタミン酸受容体サブタイプ5を介する神経伝達の遮断は膀胱収縮性及び排尿を損ねずに蓄尿を促す2012

    • Author(s)
      芳山充晴、土屋幸子、望月勉、中込宙史、宮本達也、吉良聡、武田正之
    • Organizer
      第19回日本排尿機能学会
    • Place of Presentation
      愛知県名古屋市
    • Related Report
      2012 Final Research Report
  • [Presentation] (vesicular nucleotide transporter) plays a crucial role in stretch-evoked ATP release from urothelium.2012

    • Author(s)
      Nakagomi H, Mochizuki T, Miyamoto T, Yoshiyama M, Araki I, Moriyama Y, Koizumi S, Takeda M.
    • Organizer
      American Urological Association Annual Meeting, Georgia World Congress Center
    • Place of Presentation
      Atlanta, Georgia, U.S.A.
    • Related Report
      2012 Final Research Report
  • [Presentation] Evaluation of increased voiding frequency in mice with type 2 diabetes mellitus2012

    • Author(s)
      Yoshiyama M, Mochizuki T, Nakagomi H, Miyamoto T, Takeda M
    • Organizer
      American Urological Association Annual Meeting, Georgia World Congress Center
    • Place of Presentation
      Atlanta, Georgia, U.S.A.
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規のマウス用排尿代謝ケージ構築ならびに各種パラメーターについて~野生型マウスとTRPV4ノックアウトマウスとの比較~2011

    • Author(s)
      望月勉, 他
    • Organizer
      第18回日本排尿機能学会
    • Place of Presentation
      ホテルフジタ福井(福井県福井市)
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] 遺伝性発症2型糖尿病マウスの若年期における頻尿の病態解析2011

    • Author(s)
      芳山充晴, 他
    • Organizer
      第18回日本排尿機能学会
    • Place of Presentation
      ホテルフジタ福井(福井県福井市)
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] VNUT (Vesicular Nucleotide Transporter)を介する膀胱上皮からのATP放出メカニズムの解明2011

    • Author(s)
      中込宙史, 他
    • Organizer
      第18回日本排尿機能学会
    • Place of Presentation
      ホテルフジタ福井(福井県福井市)
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] VNUT plays an important role in vesicular storage and subsequent exocytosis of ATP from bladder epithelium upon mechanical stretch stimulation2011

    • Author(s)
      Nakagomi, H., et al
    • Organizer
      International Continence Society 41^<st> Annual Meeting
    • Place of Presentation
      ScotishExhibition&conference Center (Glasgow, U.K.)
    • Year and Date
      2011-09-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Evaluations of increased voiding frequency in mice with diabetes mellitus at early stage2011

    • Author(s)
      Yoshiyama, M., et al
    • Organizer
      International Continence Society 41^<st> Annual Meeting
    • Place of Presentation
      ScotishExhibition&conference Center (Glasgow, U.K.)
    • Year and Date
      2011-09-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Risk factors of nocturia and assessment of nocturia-related quality of life in Japanese population.2011

    • Author(s)
      Imamura N, Yoda Y, Nakagomi H, Miyamoto T, Tsuchida T, Fukazawa M, Araki I, Yoshiyama M, Takeda M.
    • Organizer
      International Continence Society Meeting 41st
    • Place of Presentation
      Glasgow, U.K
    • Related Report
      2012 Final Research Report
  • [Presentation] TRPV4-deficient mice exhibit increased frequency of voiding ~evaluation of micturition behaviour using novel metabolic cage system~.2011

    • Author(s)
      Mochizuki T, Yoshiyama M, Nakagomi H, Miyamoto T, Takeda M
    • Organizer
      International Continence Society Meeting 41st
    • Place of Presentation
      Glasgow, U.K
    • Related Report
      2012 Final Research Report
  • [Presentation] Comparisons between voluntary behaviour and reflex response in control of the lower urinary tract function of mice.2011

    • Author(s)
      Yoshiyama M, Mochizuki T, Nakagomi H, Kobayashi H, Miyamoto T, Zakoji H, Takeda M.
    • Organizer
      International Continence Society Meeting 41st
    • Place of Presentation
      Glasgow, U.K
    • Related Report
      2012 Final Research Report
  • [Presentation] VNUT plays an important role in vesicular storage and subsequent exocytosis of ATP from bladder epithelium upon mechanical stretch stimulation.2011

    • Author(s)
      Nakagomi H, Mochizuki T, Miyamoto T, Kira S, Yoshiyama M, Araki I, Koizumi S, Moriyama Y, Takeda M
    • Organizer
      International Continence Society Meeting 41st
    • Place of Presentation
      Glasgow, U.K
    • Related Report
      2012 Final Research Report
  • [Presentation] Evalutations of increased voiding frequency in mice with diabetes mellitus at early stage.2011

    • Author(s)
      Yoshiyama M, Mochizuki T, Nakagomi H, Miyamoto T, Kobayashi H, Zakoji H, Takeda M.
    • Organizer
      International Continence Society Meeting 41st
    • Place of Presentation
      Glasgow, U.K
    • Related Report
      2012 Final Research Report
  • [Presentation] Risk factors of nocturia and assessment of nocturia-related quality of life in Japanese population2011

    • Author(s)
      Imamura, N., et al
    • Organizer
      International Continence Society 41^<st> Annual Meeting
    • Place of Presentation
      ScotishExhibition&conference Center (Glasgow, U.K.)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TRPV4-deficient mice exhibit increased frquency of voiding~evaluation of micturition behaviour using novel metabolic cage system~2011

    • Author(s)
      Mochizuki, T., et al
    • Organizer
      International Continence Society 41^<st> Annual Meeting
    • Place of Presentation
      ScotishExhibition&conference Center (Glasgow, U.K.)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Comparisons between voluntary behaviour and reflex response in control of the lower urinary tract function of mice2011

    • Author(s)
      Yoshiyama, M., et al
    • Organizer
      International Continence Society 41^<st> Annual Meeting
    • Place of Presentation
      ScotishExhibition&conference Center (Glasgow, U.K.)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 除脳無麻酔マウスの下部尿路活動に対するAcid-Sensing Ion Channels(ASICs)阻害薬膀胱内注入の効果.2010

    • Author(s)
      芳山充晴, 等
    • Organizer
      第17回日本排尿機能学会
    • Place of Presentation
      山梨県甲府市
    • Year and Date
      2010-10-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] 下部尿路機能研究-私の歴史2010

    • Author(s)
      芳山充晴
    • Organizer
      第17回日本排尿機能学会
    • Place of Presentation
      山梨県甲府市
    • Year and Date
      2010-09-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Gene expression patterns of acid-sensing ion channels (ASICs) families in mammalian bladder.2010

    • Author(s)
      Kobayashi H, Yoshiyama M, Inuzuka H, Kira S, Nakagomi H, Miyamoto T, Haneda Y, Sawada N, Zakoji H, Tsuchida T, Araki I, Takeda M.
    • Organizer
      International Continence Society 40th/International Uro-Gynecology Association Joint Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2012 Final Research Report
  • [Presentation] Intravesical infusion of a non-amiloride blocker of acid-sensing ion channels fails to affect lower urinary tract activity in unanesthetized decerebrate mice2010

    • Author(s)
      Yoshiyama M, Araki I, Kobayashi H, Zakoji H, Takeda M.
    • Organizer
      International Continence Society 40th/International Uro-Gynecology Association Joint Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2012 Final Research Report
  • [Presentation] Hypertension and type 2 diabetes mellitus are highly associated with nocturia than metabolic syndrome in Japanese population.2010

    • Author(s)
      Imamura N, Nakagomi H, Yoda Y, Zakoji H, Kobayashi H, Tsuchida T, Fukazawa M, Yoshiyama M, Araki I, Takeda M.
    • Organizer
      International Continence Society 40th /International Uro-Gynecology Association Joint Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2012 Final Research Report
  • [Presentation] Hypertension and type 2 diabetes mellitus are highly associated with nocturia than metabolic syndrome in Japanese population.2010

    • Author(s)
      Imamura N, et al.
    • Organizer
      International Continence Society/lntemational Uro-Gy necoiogy Association Joint Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] The effect of warm footbath before sleep on the improvement of both nocturia and nocturnal polyuria in geriatric Japanese female with bothersome nocturia-a randomized crossover study-.2010

    • Author(s)
      Kobayashi T, et al.
    • Organizer
      International Continence Society/International Uro-Gy necology Association Joint Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] Intravesical infusion of anon-amiloride blocker of acid-sensing ion channels fails to affect lower urinary tract activity in unanesthetized decerebrate mice.2010

    • Author(s)
      Yoshiyama M, et al.
    • Organizer
      International Continence Society/International Uro-Gy necology Association Joint Meeting
    • Place of Presentation
      Toronto,Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] Gene expression patterns of acid-sensing ion channels(ASICs)families in mammalian bladder.2010

    • Author(s)
      Kobayashi H, et al.
    • Organizer
      International Continence Society/International Uro-Gy necology Association Joint Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] Evaluation of increased voiding frequency in mice with type 2 diabetes mellitus

    • Author(s)
      Mitsuharu Yoshiyama
    • Organizer
      American Urological Association Annual Meeting
    • Place of Presentation
      Georgia World Congress Center(Atlanta, Georgia, U.S.A.)
    • Related Report
      2012 Annual Research Report
  • [Presentation] VNUT (vesicular nucleotide transporter) plays a crucial role in stretch-evoked ATP release from urothelium

    • Author(s)
      Hiroshi Nakagomi
    • Organizer
      American Urological Association Annual Meeting
    • Place of Presentation
      Georgia World Congress Center(Atlanta, Georgia, U.S.A.)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Vesicular nucleotide transporter (VNUT) is a key molecule for mechanosensing in the human urinary bladder: negative correlation between VNUT expression in human bladder mucosa and first desire o void

    • Author(s)
      Hiroshi Nakagomi
    • Organizer
      International Continence Society 42nd Annualmeeting
    • Place of Presentation
      China National Convention Centre(Beijing, China)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Blockade of neural transmission via metabotropic glutamate receptor subtype 5 facilitates urine storage without impairing bladder contractility and micturition in mice

    • Author(s)
      Mitsuharu Yoshiyama
    • Organizer
      International Continence Society 42nd Annualmeeting
    • Place of Presentation
      China National Convention Centre(Beijing, China)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 代謝型グルタミン酸受容体サブタイプ5を介する神経伝達の遮断は膀胱収縮性及び排尿を損ねずに蓄尿を促す

    • Author(s)
      芳山充晴
    • Organizer
      第19回日本排尿機能学会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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