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INVESTIGATIONS INTO THE MOLECULAR TARGETED THERAPY FOR OVERACTIVE BLADDER BY REGULATING INTERCELLULAR SIGNAL TRANSMISSION SYSTEM

Research Project

Project/Area Number 17390443
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

HASHITANI Hikaru  Nagoya City Univ., Grad.Sch.Med.Sci., Assistant Professor, 大学院医学研究科, 講師 (10315905)

Co-Investigator(Kenkyū-buntansha) SUZUKI Hikaru  Nagoya City Univ., Grad.Sch.Med.Sci., Professor, 大学院医学研究科, 教授 (80037548)
KUBOTA Yasue  Nagoya City Univ., Grad.Sch.Med.Sci., Research Associate, 大学院医学研究科, 助教 (00381830)
KOHRI Kanjiro  Nagoya City Univ., Grad.Sch.Med.Sci., Professor, 大学院医学研究科, 教授 (30122047)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2005: ¥11,300,000 (Direct Cost: ¥11,300,000)
KeywordsINTERSTITIAL CELL / SMOOTH MUSCLE / OVERACTIVE BLADDER / INTRACLLULARCALCIUM / PACEMAKER CELL / INTRACELLULAR CALCIUM STORE / KIT RECEPTOR / BLADDER OUTLET OBSTRUCTION / 細胞内カルシウム濃度 / ギャップ結合 / Kit免疫反応陽性細胞
Research Abstract

1. Two weeks after partial bladder outlet obstruction, population of Kit/vimentin immunoreactive interstitial cells (ICs) was increased in bladders of the guinea-pig which exhibited bladder overactivity during filling cystometry. Electron microscopy characterized ultrastructural morphology of ICs by their numerous mitochondria and close contact with each other and with neighbouring detrusor smooth muscle cells or nerves. These results suggest that the altered distribution of ICs may contribute to the pathophysiology of bladder overactivity.
2. Spontaneous Ca transients in ICs of the rabbit urethra in situ rely on both Ca release from intracellular Ca stores and Ca influx through non L-type Ca channel pathways. ICs often exhibited Ca transients synchronously with each other, but did not often show a close temporal relationship with Ca transients in urethral smooth muscle cells (USMCs), suggesting that they may not act as a coordinated pacemaker electrical network rather randomly increase … More excitability of USMCs.
3. NO caused an enhancement of spontaneous contractions in detrusor smooth muscle (DSM) of the guinea-pig bladder by spontaneous accelerating action potentials through cGMP-independent mechanisms, whilst cGMP itself has inhibitory effects on DSM contractility. Sildenafil may indirectly suppress DSM contractility by diminishing synchronicity between DSM bundles without inhibiting excitability of DSM themselves.
4. ICs in corpus cavernosum (CC) of the rabbit release prostaglandins via cyclooxygenase-2 (COX-2) activity and reinforce not only spontaneous but also nerve-mediated a-adrenergic contractions. Neurally-released NO initiates CC smooth muscle relaxations mainly by a Ca-independent mechanism but may be associated with a reduction in Ca to maintain penile erection.
5. In the guinea-pig bladder, T-type Ca channels in DSM may account for the preceding depolarizations which lead to action potentials, whilst Ca influx through these channels may couple functionally to small conductance Ca-activated K channels to stabilize the resting membrane potential. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006 2005

All Journal Article (21 results)

  • [Journal Article] A survey of commonalities relevant to function and dysfianction in pelvic and sexual organs2007

    • Author(s)
      Brading AF, Heaton JPW, Hashitani H
    • Journal Title

      International Journal of Impotence Research (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A survey of commonalities relevant to function and dysfunction in pelvic and sexual organs.2007

    • Author(s)
      Brading AF, Heaton JPW, Hashitani H
    • Journal Title

      International Journal of Impotence Research (IN PRESS)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A survey of commonalities relevant to function and dysfunction in pelvic and sexual organs2007

    • Author(s)
      Brading AF, Heaton JPW, Hashitani H
    • Journal Title

      International Journal of Impotence Research (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interaction between interstitial cells and smooth muscles in the lower urinary tract and penis2006

    • Author(s)
      Hashitani H
    • Journal Title

      The Journal of Physiology 576

      Pages: 707-714

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the rabbit urethra2006

    • Author(s)
      Hashitani H, Yanai Y, KohriK, Suzuki H
    • Journal Title

      British Journal of Pharmacology 148

      Pages: 340-349

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The role of Ni^<2+>-sensitive T-type Ca^<2+> channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder2006

    • Author(s)
      Yanai Y, Hashitani H, Kubota Y, Sasaki S, Kohri K, Suzuki H
    • Journal Title

      BJU International 97

      Pages: 182-189

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interaction between interstitial cells and smooth muscles in the lower urinary tract and penis.2006

    • Author(s)
      Hashitani H
    • Journal Title

      The Journal of Physiology 576

      Pages: 707-714

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the rabbit urethra.2006

    • Author(s)
      Hashitani H, Yanai Y, Kohri K, Suzuki H
    • Journal Title

      British Journal of Pharmacology 148

      Pages: 340-349

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The role of Ni^<2+>-sensitive T-type Ca2+ channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder.2006

    • Author(s)
      Yanai Y, Hashitani H, Kubota Y, Sasaki S, Kohri K, Suzuki H.
    • Journal Title

      BUT International 97

      Pages: 182-189

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interaction between interestitial cells and smooth muscles in the lower urinary tract and penis2006

    • Author(s)
      Hashitani H
    • Journal Title

      The Journal of Physiology 576

      Pages: 707-714

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Factors modifying the frequency of spontaneous activity in gastric muscle2006

    • Author(s)
      Suzuki H, Kito Y, Hashitani H, Nakamura E
    • Journal Title

      The Journal of Physiology 576

      Pages: 707-714

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the rabbit urethra2006

    • Author(s)
      Hashitani H, Yanai Y, Kohri K, Suzuki H
    • Journal Title

      British Journal of Pharmacology 148

      Pages: 340-309

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The role of Ni^<2+>-sensitive T-type Ca^<2+> channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder2006

    • Author(s)
      Yanai Y, Hashitani H, Kubota Y, Sasaki S, Kohri K, Suzuki H.
    • Journal Title

      BJU International 97

      Pages: 182-189

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intercellular communications within the rat anterior pituitary. XIII : An immunohistochemical and physiological study of the anterior pituitary gland of the rat2006

    • Author(s)
      Otsuka Y, HashitaniH, Shirasawa N, Sakuma E, Suzuki H, Otsuka T, Herbert DC, Soji T
    • Journal Title

      Biomedical Research 17

      Pages: 167-174

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the rabbit urethra2006

    • Author(s)
      Hashitani H., Yanai Y., Kohri K., Suzuki H.
    • Journal Title

      British Journal of Pharmacology (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The role of Ni-sensitive T-type Ca channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder2006

    • Author(s)
      Yanai Y, Hashitani H, Kubota Y, Sasaki S, Kohri K, Suzuki H.
    • Journal Title

      BJU International 97

      Pages: 182-189

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interaction between spontaneous and neurally mediated regulation of smooth muscle tone in the rabbit corpus cavemosum.2005

    • Author(s)
      Hashitani H, Yanai Y, Shirasawa N, Soji T, Tomita A, Kohri K, Suzuki H
    • Journal Title

      The Journal of Physiology 569

      Pages: 723-735

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomach.2005

    • Author(s)
      Hashitani H, Garcia-Londono AP, Hirst GDS, Edwards FR.
    • Journal Title

      The Journal of Physiology 569

      Pages: 459-465

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interaction between spontaneous and neurally mediated regulation of smooth muscle tone in the rabbit corpus cavernosum2005

    • Author(s)
      Hashitani H, Yanai Y, Shirasawa N, Soji T, Tomita A, Kohri K, Suzuki H
    • Journal Title

      The Journal of Physiology 569

      Pages: 723-735

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomach2005

    • Author(s)
      Hashitani H, Garcia-Londono AP, Hirst GDS, Edwards FR
    • Journal Title

      The Journal of Physiology 569

      Pages: 459-465

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intercellular communications within the rat anterior pituitary XII : immunohistochemicaland physiological evidences for the gap junctional coupling of the folliculo-stellate cells in the rat anterior pituitary.2005

    • Author(s)
      Sato Y, Hashitani H, Shirasawa N, Sakuma E, N aito A, Suzuki H, Asai Y, Sato G, Wada I, Herbert DC, Soji T.
    • Journal Title

      Tissue & Cell 37

      Pages: 281-291

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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