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Ca^<2+> sensitization of human and rabbit urinary bladder smooth muscle

Research Project

Project/Area Number 15591694
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SEKI Narihito  KYUSHU UNIVERSITY, UROLOGY, ASSOCIATED PROFESSOR, 大学病院, 講師 (90294941)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Junji  KYUSHU UNIVERSITY, MOLECULAR CARDIOLOGY, ASSISTANT PROFESSOR, 大学院・医学研究院, 助教授 (90237727)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsIntracellular Ca concentration / Human detrusor smooth muscle / Ca sensitization / Rho kinase / Protein kinase C / Carbachol / Human prostate / 過活動膀胱
Research Abstract

The role of Ca^<2+> sensitization in contraction of human urinary bladder smooth muscle(UBSM) was investigated.
Simultaneous measurements of intracellular Ca^<2+> concentration ([Ca^<2+>]_i) and tension in fura-2 loaded intact strips and receptor-coupled strips permeabilized with crtoxin were applied. The expressions of proteins were confirmed by western blot analysis.
In intact fura-2 loaded strips, 1 μM carbachol (CCh) induced a greater contraction and a lower [Ca^<2+>]_i elevation than that induced by 60 mM K^+ depolarization. In α-toxin permeabilized strips, 1 μM CCh induced contraction at constant [Ca^<2+>]_i and produced a leftward shift in [Ca^<2+>]_i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips, application of 3 μM Y-27632(a ROCK inhibitor) or 3 μM GF109203X (a protein kinase C(PKC) inhibitor) during the sustained phase of contraction induced by 1 μM CCh induced a relaxation without changing [Ca^<2+>]_i. In α-toxin permeabilized strips, application of 3 μM Y-27632 or 3 μM GF109203X during the sustained contraction induced by 0.3 μM Ca^<2+> plus 10 μM GTP and 1 μM CCh induced a relaxation at constant [Ca^<2+>]_i.
These results indicate that in human UBSM, CCh induces a contraction not only by increasing [Ca^<2+>]_i but also by increasing the Ca^<2+> sensitivity of the contractile apparatus in a ROCK and PKC dependent manner. Antagonism of Ca^<2+> sensitization pathways may represent an alternative target in the treatment of overactive bladder.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (5 results)

  • [Journal Article] The effects of flavoxate hydrochloride on voltage-dependent L-type Ca^<2+> currents in human urinary bladder.2005

    • Author(s)
      N Seki et al.
    • Journal Title

      Br J Pharmacol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ca^<2+> sensitization in contraction of human urinary bladder smooth muscle.2004

    • Author(s)
      N Seki et al.
    • Journal Title

      J.Urol. 172

      Pages: 748-752

    • NAID

      10019219898

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Ca^<2+> sensitization in contraction of human bladder smooth muscle.2004

    • Author(s)
      Takahashi R, Nishimura J, Hirano K, Seki N, Naito S, Kanaide H
    • Journal Title

      J Urol 172

      Pages: 748-752

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The modulation of Ca^<2+> sensitivity fegulates contractility of rabbit corpus cavernosum smooth muscle.2003

    • Author(s)
      J.Nishimura et al.
    • Journal Title

      J.Urol. 169

      Pages: 2412-2416

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of MCC-134 on the ATP-sensitive K^+ channels in pig urethra.2003

    • Author(s)
      N Seki et al.
    • Journal Title

      Eur.J.Pharmacol. 482(1-3)

      Pages: 287-295

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Holmium laser enucleation for prostatic adenoma : analysis of learing curve over the course of consecutive 70 patients.2003

    • Author(s)
      N Seki et al.
    • Journal Title

      J.Urol. 170

      Pages: 1847-1850

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] The effects of MCC-134 on the ATP-sensitive K^+ channels in pig urethra.2003

    • Author(s)
      Yunoki T, Teramoto N, Takano N, Seki N, Creed KE, Naito S, Ito Y
    • Journal Title

      Eur J Pharmacol 482(1-3)

      Pages: 287-295

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Holmiura laser enucleation for prostatic adenoma : analysis of learning curve over the course of 70 consecutive cases.2003

    • Author(s)
      Seki N, Mochida O, Kinukawa N, Sagiyama K, Naito S
    • Journal Title

      J Urol 170(5)

      Pages: 1847-1850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The modulation of Ca^<2+> sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle.2003

    • Author(s)
      Takahashi R, Nishimura J, Hirano K, Naito S, Kanaide H
    • Journal Title

      J.Urol 169

      Pages: 2412-2416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The modulation of Ca^<2+> sensitivity regulates contractility of rabbit corpus2003

    • Author(s)
      J.Nishimura et al.
    • Journal Title

      J.Urol. 169

      Pages: 2412-2416

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Protein kinase network in the regulation of phosphorylation and dephosphorylation of smooth muscle myosin light chain.2003

    • Author(s)
      J.Nishimura et al.
    • Journal Title

      Mol.Cell.Biochem. 248

      Pages: 105-114

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The effects of flavoxate hydrochloride on voltage-dependent L-type Ca^<2+> currents in human urinary bladder.

    • Author(s)
      Tomoda T, Aishima M, Takano N, Nakano T, Seki N, Yonemitsu Y, Sueishi K, Naito S, Ito Y, Teramoto N
    • Journal Title

      Br J Pharmacol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] J.Nishimura, et al.: "The modulation of CA^<2+> sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle"Journal of Urology. 169. 2412-2416 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Nishimura, et al.: "Ca^<2+> sensitization in contraction of human urinary bladder smooth muscle"Journal of Urology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] N Seki, et al.: "The effects of MCC-134 on the ATP-sensitive K^+ channels in pig urethra"European Journal of Pharmacology. 482(1-3). 287-295 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Nishimura, et al.: "Protein kinase network in the regulation of phosphorylation and dephosphorylation of smooth muscle myosin light chain"Mol.Cell.Biochem.. 248. 105-114 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N Seki, et al.: "Holmium laser enucleation for prostatic adenoma : analysis of learning curve over the course of consecutive 70 patients"Journal of Urology. 170. 1847-1850 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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