Functional analyses of human prostate smooth muscle- Strategy for development of new drugs for benign prostatic hyperplasia

• Project/Area Number: 21791518
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: TAKADA Masa Nagoya City University, 大学院・医学研究科, 研究員 (60468254)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 前立腺平滑 / α1受容体 / NO / 細胞内カルシウム濃度

Research Abstract

We examined the cellular mechanisms of human prostate contraction by using prostate biopsy specimens. Phenylephrine increased the amplitude and the frequency of the spontaneous contractions. SIN-1 decreased the excitability. Nifedipine blocked all spontaneous contractions. Cyclopoazonic acid caused a transient excitation followed by blockade of all contractions. Charybdotoxin increased the excitability due to blockade of BK channels probably causing an increase of action potential discharge. From these results, we suggest that spontaneous contractions of human prostate depend on both the influx of calcium through L type calcium channels and calcium release from the sarcoplasmic reticulum. BK channel openings were inhibitory in terms of excitation of human prostate smooth muscle. Prostate biopsy specimens are a useful means of investigating the mechanisms of human prostate contraction and development of new drugs for benign prostatic hyperplasia.

Research Products

• [Journal Article] New pharmacologic horizons in the treatment of benign prostatic hyperplasia. (2010)
  • Author(s): Kojima Yoshiyuki, Hayase Masa, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: Current Drug Therapy 5 Pages: 262-270
  • Peer Reviewed
• [Journal Article] Role of K^+ channels in regulating spontaneous activity in detrusor smooth muscle in situ in the mouse bladder. (2009)
  • Author(s): Hayase Masa, Hashitani Hikaru, Kohri Kenjiro, Suzuki Hikaru
  • Journal Title: The Journal of Urology 181 Pages: 2355-2365
  • Peer Reviewed
• [Journal Article] Beyond the Abstract-Subtypes of alpha(1)-adrenoreceptors in BPH : future prospects for personalized medicine. (2009)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Shibata Yasuhiro, Imura Makoto, Hayase Masa, Okada Shinsuke, Kubota Yasue, Hayashi Yutaro, Tsujimoto Gozoh, Kohri Kenjiro
  • Journal Title: UroToday
  • Peer Reviewed
• [Journal Article] Role of K+ channels in regulating spontaneous activity in detrusor smoth muscle in situ in the mouse bladder. (2009)
  • Author(s): Hayase Masa
  • Journal Title: The Journal of Urology 181(5) Pages: 2355-2365
  • Peer Reviewed
• [Presentation] 前立腺肥大症に対するα1遮断薬の長期有効性の予測因子 (2010)
  • Author(s): 小島祥敬、柴田泰宏、井村誠、早瀬麻沙、窪田泰江、佐々木昌一、林祐太郎、郡健二郎
  • Organizer: 第60回日本泌尿器科学会中部総会
  • Place of Presentation: 名古屋市
• [Presentation] Correlation between expression of alpha1-adrenoceptor subtype mRNA and severity of lower urinary tract symptoms or bladder outlet obstruction in benign prostatic hyperplasia patients. (2010)
  • Author(s): Kojima Yoshiyuki, Shibata Yasunori, Imura Makoto, Hayase Masa, Kubota Yasue, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: Annual Meeting of the International Continence Society
  • Place of Presentation: Toronto (Canada)
• [Presentation] マウス膀胱平滑筋の自発活動制御におけるK channelの役割。 (2009)
  • Author(s): 早瀬麻沙(高田麻沙 旧姓を使用)
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山コンベンションセンター(岡山市)
  • Year and Date: 2009-04-16
• [Presentation] Prostate growth inhibition by subtype-selective alpha1-adrenoceptor antagonist naftopidil in benign prostatic hyperplasia. (2009)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Oda Nobuyuki, Hayase Masa, Kubota Yasue, Hayashi Yutaro, Kiniwa Mamoru, Kohri Kenjiro
  • Organizer: AUA 2009 Annual Meeting
  • Place of Presentation: Chicago (USA)