The interaction between RHO/ROCK and NO in the urothelium and the role of muscarinic receptor subtype for detrusor contraction

• Project/Area Number: 22591801
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Dokkyo Medical University
• Principal Investigator: YAMANISHI Tomonori 獨協医科大学, 医学部, 教授 (90220425)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ムスカリン / Rho / ROCK / カルバコール / ピロカルピン / Y27632 / ファスジル / 一酸化窒素 / 膀胱 / 排尿筋 / 尿路上皮 / NO合成酵素 / Rho kinase

Research Abstract

Cumulative concentration-response curves (CRCs) to cholinergic agonists (carbachol and pilocarpine) were obtained in the human and porcine detrusor tissues with and without urothelium. After the first curve, the second CRCs to cholinergic agonists were obtained in the presence of ROCK inhibitors (Y27632、fasudil). After administration ofROCK inhibitors decrease of maximum contraction (Emax) was greater in detrusor tissues with urothelium than those without urothelium. Then CRCs to carbachol were obtained in the presence of 30 μM L-NAME plus 30 μM Y-27632. There was a significant difference with regard to Emax between the control and tissues in the presence of Y-27632 and in the presence of L-NAME plus Y-27632. However no significant difference was noted between Emax in tissues with Y-27632 and in that with L-NAME plus Y-27632.

Research Products

• [Journal Article] Randomized, single-blind, parallel study of the effectiveness and safety of solifenacin versus propiverine in the treatment of overactive bladder (2013)
  • Author(s): Fukuda T, Yamanishi T, Uchiyama T, Kamai T
  • Journal Title: LUTS Pages: 11-16
  • Peer Reviewed
• [Journal Article] Analysis of energy loss mediated by an alpha-1 blocker in patients with benign prostatic hyperplasia using a virtual urethra processed from an endoscopic video image (2012)
  • Author(s): T. Sazuka
  • Journal Title: Journal of Endourology Volume: 26 Issue: 9 Pages: 1216
  • DOI: 10.1089/end.2012.0078
  • URL: https://pure.teikyo.jp/en/publications/93c88015-cef1-4341-84fa-3cb7c6c50d40
  • Peer Reviewed
• [Journal Article] 下部尿路における・-アドレナリン受容体サブタイプの役割 (2012)
  • Author(s): 山西友典、榊原隆次、内山智之
  • Journal Title: 自律神経 Volume: 49 Pages: 216-218
• [Journal Article] SINPHONI (Study of Idiopathic Normal Pressure Hydrocephalus On Neurological Improvement). Correlation of right frontal hypoperfusion and urinary dysfunction in iNPH: a SPECT study. (2012)
  • Author(s): Sakakibara R
  • Journal Title: Neurourology and Urodynamics Volume: 31 Pages: 50-55
  • Peer Reviewed
• [Journal Article] Receiver operating characteristic analysis of sphincter electromyography for parkinsonian syndrome. (2012)
  • Author(s): Yamamoto T
  • Journal Title: Neurourology and Urodynamics Volume: 31 Pages: 1128-1134
  • Peer Reviewed
• [Journal Article] Analysis of energy loss mediated by an alpha-1 blocker in patients with benign prostatic hyperplasia using a virtual urethra processed from an endoscopic video image. (2012)
  • Author(s): Sazuka T
  • Journal Title: J Endourology Volume: 26 Pages: 1216-1220
  • Peer Reviewed
• [Journal Article] Randomized, single-blind, parallel study of the effectiveness and safety of solifenacin versus propiverine in the treatment of overactive bladder. (2012)
  • Author(s): Fukuda T
  • Journal Title: Lower Urinary Tract Symptoms Volume: 5 Pages: 11-16
  • Peer Reviewed
• [Journal Article] 各種排尿・性機能スコアの妥当性.過活動膀胱質問票(OAB-q) (2012)
  • Author(s): 山西友典
  • Journal Title: 排尿障害プラクティス Volume: 20 Pages: 69-75
• [Journal Article] Pulsed magnetic stimulation with a high-frequency continuous magnetic stimulator (SMN-X) does not exert an adverse effect on genital organs and the estrous cycle in female Iar:Wistar-Imamichi rats (2011)
  • Author(s): Sato E
  • Journal Title: Neurourol Urodyn. Volume: 30 Issue: 8 Pages: 1675-1680
  • DOI: 10.1002/nau.21126
  • Peer Reviewed
• [Journal Article] 安全性に配慮した過活動膀胱治 療 (2011)
  • Author(s): 山西友典
  • Journal Title: Physicians ' therapy manual Volume: 7 Pages: 1343-3598
• [Journal Article] 男性過活動膀胱の治療.「特集:頻尿・切迫性尿失禁の治療」 (2011)
  • Author(s): 山西友典
  • Journal Title: 臨床泌尿器 Volume: 65 Pages: 731-737
• [Journal Article] Role of urodynamic studies in the diagnosis and treatment of lower urinary tract symptoms (2011)
  • Author(s): Yamanishi T, Sakakibara R, Uchiyama T, Hirata K
  • Journal Title: Urological Science Volume: 22 Pages: 120-128
  • Peer Reviewed
• [Journal Article] Pelvic organ dysfunction is more prevalent and severe in MSA-P compared to parkinson's disease (2011)
  • Author(s): Yamamoto T, et al
  • Journal Title: Neurourol Urodynam Volume: 30 Issue: 1 Pages: 102-107
  • DOI: 10.1002/nau.20948
  • Peer Reviewed
• [Journal Article] Levodopa ameliorated anorectal constipation in de novo Parkinson's disease : The QL-GAT study (2011)
  • Author(s): Tateno F, et al
  • Journal Title: Parkinsonism Relat Disord Volume: 17 Pages: 662-666
  • Peer Reviewed
• [Journal Article] Efficacy of tolterodine ER for the treatment of neurogenic detrusor overactivity and/or low compliance bladder. (2010)
  • Author(s): Watanabe M, Yamanishi T
  • Journal Title: Int J Urol Volume: 17 Issue: 11 Pages: 931-6
  • DOI: 10.1111/j.1442-2042.2010.02635.x
  • Peer Reviewed
• [Journal Article] Randomized, placebo-controlled study of electrical stimulation with pelvic floor muscle training for severe urinary incontinence after radical prostatectomy (2010)
  • Author(s): Yamanishi T
  • Journal Title: J Urol Volume: 184 Issue: 5 Pages: 2007-12
  • DOI: 10.1016/j.juro.2010.06.103
  • Peer Reviewed
• [Journal Article] 同効薬剤の選択-そのエビデンスと実際-抗コリン薬 (2010)
  • Author(s): 山西友典、本田幹彦、吉田謙一郎
  • Journal Title: 泌尿外 Volume: 23 Pages: 413-414
• [Journal Article] Randomized, placebo-controlled study of electrical stimulation with pelvic floor muscle training for severe urinary incontinence after radical prostatectomy. (2010)
  • Author(s): Yamanishi T, et al
  • Journal Title: The Journal of Urology Volume: 184 Pages: 2007-2012
  • Peer Reviewed
• [Journal Article] Efficacy of tolterodine ER for the treatment of neurogenic detrusor over activity and/or low compliance bladder. (2010)
  • Author(s): Watanabe M, Yamanishi T, et al
  • Journal Title: International Journal of Urology Volume: 17 Pages: 931-936
  • Peer Reviewed
• [Presentation] The effect of L-NG-Nitroarginine Methyl Ester (L-NAME) on relaxation induced by Y 27632, a Rho-kinase inhibitor, in the porcine urinary bladder with intact urothelium (2013)
  • Author(s): Yamanishi T, Fuse M, Shibata C, Uchiyama T
  • Organizer: 43th Annual meeting of the International Continence Society
  • Place of Presentation: Barcerona
• [Presentation] Efficacy and safety of pilocarpine hydrochloride in the treatment of voiding difficulty in patients with detrusor underactivity (2013)
  • Author(s): Fuse M, Yamaguchi C, Uchiyama T, Kamai T, Yamanishi T
  • Organizer: 38th Annual Meeting of the International Urogynecological Association
  • Place of Presentation: Dublin
• [Presentation] ヒトおよびブタの膀胱平滑筋収縮に対するムスカリンアゴニスト pilocarpineの効果 (2013)
  • Author(s): 布施美樹、山口千晴、内山智之、釜井隆男、山西友典
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌
• [Presentation] The effect of L-NG-Nitroarginine Methyl Ester (L-NAME) on relaxation induced by Y 27632, a Rho-kinase inhibitor, in the porcine urinary bladder with intact urothelium (2013)
  • Author(s): Yamanishi T
  • Organizer: International Continence Society
  • Place of Presentation: Barcerona
• [Presentation] Influences of imidafenacin on cognitive function in patients with overactive bladder. (2012)
  • Author(s): Sakakibara R
  • Organizer: 42nd Annual meeting of the International Continence Society
  • Place of Presentation: Beijing
• [Presentation] The effects of pirocarpine, a muscarinic receptor agonist, on contraction of the urinary bladder in the pig and human (2012)
  • Author(s): Yamanishi T
  • Organizer: The 32nd Congress of Societe Internationale d'Urologie
  • Place of Presentation: Fukuoka
• [Presentation] Single-blind, randomized controlled study of a high-frequency continuous magnetic stimulator and sham stimulation in patients with urgency incontinence. (2012)
  • Author(s): Yamanishi T
  • Organizer: Societe Internationale d’Urologie
  • Place of Presentation: Fukuoka
• [Presentation] The effects of pirocarpine, a muscarinic receptor agonist, on contraction of the urinary bladder in the pig and human. (2012)
  • Author(s): Yamanishi T
  • Organizer: Societe Internationale d’Urologie
  • Place of Presentation: Fukuoka
• [Presentation] Multicenter, randomized placebo-controlled study of the efficacy of a high-frequency continuous magnetic stimulator for the treatment of urinary incontinence in women with overactive bladder (2012)
  • Author(s): Yamanishi T
  • Organizer: Pan-Pacific Continence Society
  • Place of Presentation: Nagoya
• [Presentation] Long-Term Efficacy of Silodosin for the Treatment of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (2012)
  • Author(s): Yamanishi T
  • Organizer: International Continence Society
  • Place of Presentation: Beijing
• [Presentation] A cross-sectional survey of overactive bladder in Japanese outpatients in daily practice. (2012)
  • Author(s): Yamanishi T
  • Organizer: International Urogynecological Association
  • Place of Presentation: Brisbane
• [Presentation] The effect of pilocarpine, an M3-muscarinic receptor agonist, on contraction of the porcine urinary bladder in vitro (2011)
  • Author(s): Yamanishi T,Yoshida K
  • Organizer: 41st Annual Meeting of the International Continence Society
  • Place of Presentation: Glasgow, UK
• [Presentation] The effects of pilocarpine, an M3-musucarinic receptor agonist on contraction of the human urinary bladder in vitro (2011)
  • Author(s): Yamanishi T,Yoshida K
  • Organizer: 36th Annual Meeting of the International Urogynecological Association
  • Place of Presentation: Lisbon
• [Presentation] Comparison of the effects of silodosin and tamsulosin for the treatment of benign prostatic hyperplasia (2011)
  • Author(s): Yamanishi T, et al
  • Organizer: 41st Annual Meeting of the International Continence Society
  • Place of Presentation: Glasgow
• [Presentation] The effect of pilocarpine, an M3-muscarinic receptor agonist, on contraction of the porcine urinary bladder in vitro (2011)
  • Author(s): Yamanishi T, et al
  • Organizer: 41st Annual Meeting of the International Continence Society
  • Place of Presentation: Glasgow
• [Presentation] 前立腺肥大症に対する薬物治療:プロッカーと抗写リン薬を中心に (2010)
  • Author(s): 山西友典
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-28
• [Book] 過活動膀胱ガイドライン「今日の治療指針2012年版」第53巻 (山口徹、北原光夫、福井次矢、編) (2012)
  • Author(s): 山西友典
  • Publisher: 医学書院 東京
• [Book] 今日の治療指針 (2012)
  • Author(s): 山西友典
  • Publisher: 医学書院
• [Book] 日本泌尿器科学会前立腺肥大症診療ガイドライン委員会編. 前立腺肥大症診療ガイドライン (2011)
  • Author(s): 本間之夫、石塚修、大園誠一郎、賀本敏行、河内明弘、後藤百万、関成人、永井敦、舛森直哉、山西友典、横山修
  • Publisher: リッチヒルメディカル 東京
• [Book] 過活動膀胱ガイドライン「今日の治療指針2011年版」第53巻 (山口徹、北原光夫、福井次矢、編) (2011)
  • Author(s): 山西友典
  • Publisher: 医学書院 東京
• [Book] 前立腺肥大症診療ガイドライン (2011)
  • Author(s): 本間之夫, 他
  • Total Pages: 132
  • Publisher: リッチヒルメディカル
• [Book] 過活動膀胱ガイドライン 今日の治療指針 (2010)
  • Author(s): 山西友典
  • Total Pages: 5
  • Publisher: 医学書院