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2005 Fiscal Year Final Research Report Summary

Novel physiological function of CLC-5 chloride channel associated with gastric proton pump

Research Project

Project/Area Number 15390062
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionUniversity of Toyama (2005)
Toyama Medical and Pharmaceutical University (2003-2004)

Principal Investigator

SAKAI Hideki  University of Toyama, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60242509)

Project Period (FY) 2003 – 2005
Keywordsgastric acid secretion / chloride ion / ion channel / CLC-5 / proton pump / molecular association / EP / phosphorylation
Research Abstract

In gastric parietal cells, protons are actively secreted by gastric proton pump (H.K-ATPase), but it has not been established what molecule contributes to apical Cl^- transport for HCl secretion. Although CLC-2 was suggested to be a candidate for the apical Cl^- channel, we found here that no CLC-2 protein is expressed in the gastric parietal cells. Interestingly, CLC-5 was found to be expressed in the parietal cells.
In the present study, we studied about the physiological function of CLC-5 in the parietal cells. We found that CLC-5 protein is co-localized with gastric H,K-ATPase in the tubulovesicles and the apical membrane of the parietal cells. Immunoprecipitation using the anti-H,K-ATPase antibody showed the association between CLC-5 and H,K-ATPase in isolated hog gastric vesicles. We succeeded to establish the tetracycline-regulated stable expression of CLC-5 in the HEK293 cells that stably express H,K-ATPase α- and β-subunits. When the cells were treated with tetracycline, CLC-5 was expressed in the plasma membrane and intracellular organelles, while no significant expression of CLC-5 was observed in the cells treated without tetracycline. CLC-5 was co-localized with gastric H,K-ATPase in the plasma membrane of the tetracycline-treated cells. In these cells, the expression of CLC-5 significantly increased the activity of H,K-ATPase, ^<86>Rb^+ transport and phosphorylation level (EP level) of the H,K-ATPase. In the cell surface biotinylation of H,K-ATPase α-subunit, we found that the expression of CLC-5 did not affect the expression level of H,K-ATPase in the plasma membrane. These results suggest that CLC-5 acts as a novel up-regulator of gastric H,K-ATPase.

  • Research Products

    (14 results)

All 2005 2004 2003

All Journal Article (14 results)

  • [Journal Article] Cyclic AMP-dependent Cl^- secretion induced by thromboxane A_2 in isolated human colon.2005

    • Author(s)
      Naoki HORIKAWA et al.
    • Journal Title

      Journal of Physiology (London) 562巻3号

      Pages: 885-897

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel molecular mechanisms of gastric phospholipids translocation activity in isolated hog gastric vesicles.2005

    • Author(s)
      Magotoshi MORII et al.
    • Journal Title

      Membrane 30巻6号

      Pages: 312-317

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cyclic AMP-dependent Cl^- secretion induced by thromboxane A_2 in isolated human colon.2005

    • Author(s)
      Horikawa N, et al.
    • Journal Title

      Journal of Physiology (London) 562

      Pages: 885-897

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel molecular mechanisms of gastric phospholipids translocation activity in isolated hog gastric vesicles.2005

    • Author(s)
      Morii M, et al.
    • Journal Title

      Membrane 30

      Pages: 312-317

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Leukotrienes-mediated effects of water extracts from Sargassum horneri, a marine brown alga, on Cl^- absorption in isolated rat colon.2004

    • Author(s)
      Hideki SAKAI et al.
    • Journal Title

      Japanese Journal of Physiology 54巻1号

      Pages: 71-77

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Up-regulation of Na^+,K^+-ATPase α3-isoform and down-regulation of theα1-isoform in human colorectal cancer.2004

    • Author(s)
      Hideki SAKAI et al.
    • Journal Title

      FEBS Letters 563巻1-3号

      Pages: 151-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Is the CIC-2 chloride channel involved in the Cl^- secretory mechanism of gastric parietal cells?2004

    • Author(s)
      Katsuhito HORI et al.
    • Journal Title

      FEBS Letters 575巻1-3号

      Pages: 105-108

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association of paracellin-1 with ZO-1 augments the reabsorption of divalent cations in renal epithelial cells.2004

    • Author(s)
      Akira IKARI et al.
    • Journal Title

      Journal of Biological Chemistry 279巻52号

      Pages: 54826-54832

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Leukotrienes-mediated effects of water extracts from Sargassum horneri, a marine brown alga, on Cl^- absorption in isolated rat colon.2004

    • Author(s)
      Sakai H, et al.
    • Journal Title

      Japanese Journal of Physiology 54

      Pages: 71-77

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Up-regulation of Na^+,K^+-ATPase α3-isoform and down-regulation of the α1-isoform in human colorectal cancer.2004

    • Author(s)
      Sakai H, et al.
    • Journal Title

      FEBS Letters 563

      Pages: 151-154

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Is the ClC-2 chloride channel involved in the Cl^- secretory mechanism of gastric parietal cells?2004

    • Author(s)
      Hori K, et al.
    • Journal Title

      FEBS Letters 575

      Pages: 105-108

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association of paracellin-1 with ZO-1 augments the reabsorption of divalent cations in renal epithelial cells.2004

    • Author(s)
      Ikari A, et al.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 54826-54832

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of small-conductance Cl^- channels by the interleukin-1β-stimulated production of superoxide in rabbit gastric parietal cells.2003

    • Author(s)
      Hideki SAKAI et al.
    • Journal Title

      Journal of Physiology (London) 551巻1号

      Pages: 207-217

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibition of small-conductance Cl^- channels by the interleukin-1β-stimulated production of superoxide in rabbit gastric parietal cells.2003

    • Author(s)
      Sakai H, et al.
    • Journal Title

      Journal of Physiology (London) 551

      Pages: 207-217

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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