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Elucidation of central mechanisms of micturition reflex for developing novel medicine of micturition disorder, especially a reinforcement drug of micturition reflex

Research Project

Project/Area Number 13672392
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKumamoto University

Principal Investigator

TAKAHAMA Kazuo  Faculty of Pharmaceutical Sciences, Kumamoto University. Department of Hygienic Chemistry, Professor, 薬学部, 教授 (80150548)

Co-Investigator(Kenkyū-buntansha) TANAKA Hideaki  Division of Developmental Neurobiology, Graduate School of Medical Sciences, Kumamoto University, Professor, 大学院・医学研究科, 教授 (90106906)
SHIRASAKI Tetsuya  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Associate Professor, 薬学部, 助教授 (30264047)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsmicturition reflex / glycine receptor / dextromethorphan / periaqueductal gray / cystometry / Fos protein / Barington's nucleus / Patch clamp / 中脳水道周囲灰白質 / FOS蛋白質 / DiI / 多連微小ピペット / ラット / 排尿障害 / Z-グリシナミド / 膀胱収縮
Research Abstract

In this project, we investigated whether glycine receptors are involved in central mechanisms of micturition reflex in rats. Rats (S.D., 250-300g) under anesthesia with urethane (0.96 mg/kg, i.p.) were used in all in vivo experiments. Single neurons of the brain were acutely dissected from 9-14 days of Wistar rat. 【Results】 1) Dextromethorphan (DM, 5-10 mg/kg, i.v.) suppressed the bladder and urethral pressure. 2) A glycine prodrug, z-glycinamide (50-100 mg/kg, i.p.) induced rhythmic bladder contractions in a dose-dependent manner. The mean number of contractions in z-glycinamide treated group was 22.2±2.6 for 40 min. this value was significantly higher than that in control group (7.5±2.3). 3) In cystometrogram, i.c.v. administration of glycine at 100μg but not 9μg significantly reduced the capacity of the bladder. 4) Direct administration of glycine 3μg into the caudal region of periaqueductal gray matter (PAG) (-8300〜-8800μm, from bregma) facilitated micturition reflex as indicated by an increase in maximal bladder pressure and a decrease in a threshold of micturition reflex. But injection of the same dose of glycine into the rostal region of the PAG had little influence on the reflex. 5) In the whole region of the PAG, expression of glycine receptor α-subunit mRNA was confirmed. 6) Tracing study of neuronal circuits using DiI showed neurons in the caudal PAG projected to the region Me5 in the midbrain and the area postrema in the medulla oblongata. 7) Patch-clamp study showed that glycine caused strychnine-sensitive current in single neurons dissected from the whole region of the Barington's nucleus. 8) Infusion of acetic acid solution into the bladder expressed Fos protein in the micturition center and related nuclei. DM strongly inhibited the Fos protein expression in the Barington's nucleus and several regions involved in micturition reflex. These results suggest that glycine receptors may be involved partly in central mechanisms of micturition reflex.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Maruyama I., Okabe Y., Shirasaki T., Ishibashi H., Takahama K.: "Are glycine receptors involved in micturition reflex?"Jpn.J.Pharmacol.. 85. 240 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, K., Shirasaki, T., Soeda, F., Takahama, K.: "Glycine responsiveness of neurons in Barringto's nucleus, a micturition center in rat"J.Pharmacol.Sci.. 91. 222 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honda, A., Soeda, F., Shirasaki, T., Tanaka, A., Takahama, K.: "Effects of dextromethorphan (DM) and strychnine (Str) on bladder irritation-induced Fos-like protein (FLP) expression in the brainstem and spinal cord of rats"J.Pharmacol.Sci.. 91. 212 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiradaki, T., Yamasaki, K., Tanaka, A., Soeda, F., Takahama, K.: "Glycine-induce currents in acutely dissociated rat Barington's nucleus neurons"Neuroscinece. (Sbmitted). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高濱和夫: "「薬局」 頻尿・尿失禁治療薬の薬理"南江堂. 8 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maruyama, I., Y. Okabe, T. Shirasaki, H. Ishibashi, K. Takahama: "Are glycine receptors involved in micturition reflex?"Jpn. J. Pharmacol.. 85. 240 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahama K.: "Micturition reflex and 5-HT_<1A> and glycine receptor"Folia Pharmacol. Japon.. 118. 73 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, K., T. Shirasaki, F. Soeda, K. Takahama: "Glycine responsiveness of neurons in Barington's nucleus, a micturition center in rat"J. Pharmacol. Sci.. 91. 222 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honda, A., F. Soeda, T. Shirasaki, H. Tanaka, K. Takahama: "Effects of dextromethorphan (DM) and strychnine (Str) on bladder imitation-induced Fos-like protein (FLP) expression in the brainstem and spinal cord of rats"J. Pharmacol. Sci.. 91. 212 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shirasaki T., K. Yamasaki, A. Tanaka, F. Soeda, K. Takahama: "Glycine-induce currents in acutely dissociated rat Barington's nucleus neurons"Neuroscience. submitted. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 岡部裕一: "中脳水道中心灰白質へのグリシンの微量注入は排尿反射を促進させるか?"日本排尿機能学会誌. 13巻・1号. 110 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本田 淳: "膀胱内侵害刺激による下位脳幹および脊髄におけるFos蛋白の発現に対するデキストメトルファンの作用"日本排尿機能学会誌. 13巻・1号. 111 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Atsushi Honda: "Effect of dextromethorphan (DN) and strychnine (Str) on bladder irritation-induced Foslike protein (FLP) expression in the brainstem and spinal cord of rats"Journal of Pharmacological Sciences. 91(Suppl.I). 212 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koudai Yamasaki: "Glycine responsiveness of neurons in Barrington's nucleus, a micturition center in rat"Journal of Pharmacological Sciences. 91(Suppl.I). 222 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高濱和夫: "薬局 53巻・8号"頻尿・尿失禁治療薬の薬理. 21-28 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 岡部裕一, 丸山 格, 山本 巌, 副田二三夫, 白崎哲哉, 高濱和夫: "排尿反射の中枢内神経伝達機序に関する研究の-グリシンおよび関連物質排尿反射に対する作用-"日本薬理学雑誌. 119・No.3. 20 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高濱和夫, 白崎哲哉: "排尿反射と5-HT_<1A>およびグリシン受容体"日本薬理学雑誌. 118・No.1. 73 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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