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Fundamental research for an inhalational therapy using hyposmotic solution to stimulate airway ciliary motility

Research Project

Project/Area Number 16590169
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOsaka Medical College

Principal Investigator

NAKAHARI Takashi  Osaka Medical College, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20189020)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsairway epithelia / mucrociliary clearance / cilia / ATP / ciliary beat frequency (CBF) / video micoscopy / trachea / bronchiole / tracea / ciliary beat frequency (CBF) / purinergic receptor / hypo-osmotic stress / osmotic swelling / cetylcholine
Research Abstract

The ciliary beat frequency (CBF) of rat tracheal ciliary cells in a slice preparation was measured using video-enhanced contrast (VEC) microscopy. Acetylcholine (ACh) or ATP increased CBF mediated via intracellular Ca^<2+> concentration ([Ca^<2+>]_i) in a dose-dependent manner. An adequate hypo-osmotic stress (-40mosM) potentiated ACh-stimulated CBF increase in tracheal ciliary cells. The present study demonstrated that suramin (an inhibitor of purinergic receptors) and apyrase (an ATPase/ADPase) eliminate the hypo-osmotic potentiation of ACh-stimulated CBF increase and that ATP potentiates ACh-stimulated rises in [Ca^<2+>]_i and CBF increase. A hypo-osmotic stress (-40mosM) transiently increased [Ca^<2+>]_i and potentiated the ACh-stimulated [Ca^<2+>]_i increase. The hypo-osmotic potentiation of ACh-stimulated CBF increase was not detected under Ca^<2+>-free conditions. These observations suggest that a hypo-osmotic stress stimulates ATP release from the trachea. The released ATP may induce further increases in [Ca^<2+>]_i and CBF in ACh-stimulated tracheal ciliary cells, which may be mediated by purinergic receptors. On the other hand, in distal airway ciliary cells (lung slice) unlike trachea, ACh or ATP did not increase CBF and [Ca^<2+>]_i, although a Ca^<2+>-free solution decreased CBF, and ionomycin (5μM) or thapsigargin (2μM) increased it. Terbutaline (10μM), a selective β_2-adrenergic agonist, increased CBF in both tracheal and distal airway ciliary cells. These observations suggest that the Ca^<2+>-mobilization mechanisms via purinergic or muscarinic receptors of the distal airway ciliary cell may be different from those of the tracheal ciliary cell. Thus, the CBF increase is differently regulated in the tracheal and distal airway epithelia of the rat.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (22 results)

All 2006 2005 2004 Other

All Journal Article (22 results)

  • [Journal Article] Enhancement of Ca^2+ -regulated exocytosis by indomethacin in guinea-pig antral mucous cells : arachidonic acid accumulation.2006

    • Author(s)
      Fujiwara S, Shimamoto C, Nakanishi Y, Katsu K, Kato M, Nakahari T.
    • Journal Title

      Experimental Physiology 91.1

      Pages: 249-259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice.2006

    • Author(s)
      Takaki E, 他
    • Journal Title

      Journal of Bioloical Chemistry (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] CyclicGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells2006

    • Author(s)
      Saad AH, Shimamoto C, Nakahari T, Fujiwara S, Katus K, Marunaka Y
    • Journal Title

      American Journal of Physiology Gastrointestinal Liver Physiology (in press)

    • NAID

      130005448316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Enhancement of Ca2+-regulated exocytosis by indomethacin in guinea-pig antral mucous cells : arachidonic acid accumulation.2006

    • Author(s)
      Fujiwara S, Shimamoto C, Nakanishi Y, Katsu K, KatoM, Nakahari T.
    • Journal Title

      Experimental Physiology 91.1

      Pages: 249-259

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhancement of Ca^<2+>-regulated exocytosis by indomethacin in guinea-pig antral mucous cells : arachidonic acid accumulation.2006

    • Author(s)
      Fujiwara S, Shimamoto C, Nakanishi Y, Katsu K, Kato M, Nakahari T.
    • Journal Title

      Experimental Physiology 91.1

      Pages: 249-259

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of ACh-stimulated exocytosis by NSAIDs in guinea pig antral mucous cells : autocrine regulation of mucin secretion by PGE22005

    • Author(s)
      Shimamoto C, Fujiwara S, Kato M, Ito S, Katsu K, Mori H, Nakahari T.
    • Journal Title

      American Journal of Physiology Gastrointestinal Liver Physiology 288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Cell shrinkage evoked by Ca^2+ -free solution in rat alveolar type II cells : Ca^2+ regulation of Na^+ -H^+ exchange.2005

    • Author(s)
      Murao H, Yoshida H, Nakahari T.他
    • Journal Title

      Experimental Physiology 90.2

      Pages: 203-213

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ATP regulation of ciliary beat frequency in rat tracheal and distal airway epithelium.2005

    • Author(s)
      Hayashi T, Kawakami M, Sasaki S, Katsumata T, Mori H, Yoshida H, Nakahari T.
    • Journal Title

      Experimental Physiology 90.4

      Pages: 535-544

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Inhibition of ACh-stimulated exocytosis by NSAIDs in guinea pig antral mucous cells : autocrine regulation of mucin secretion by PGE2.2005

    • Author(s)
      Shimamoto C, Fujiwara S, Kato M, Ito S, Katsu K, Mori H, Nakahari T.
    • Journal Title

      American Journal of Physiology Gastrointestinal Liver Physiology 288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell shrinkage evoked by Ca2+-free solution in rat alveolar type II cells : Ca2+ regulation of Na+-H+ exchange.2005

    • Author(s)
      Murao H, Shimizu A, Hosoi K, Iwagaki A, Min K-Y, Kishima G, Hanafusa T, Kubota T, Kato M, Yoshida H, Nakahari T.
    • Journal Title

      Experimental Physiology 90.2

      Pages: 203-213

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell shrinkage evoked by Ca^<2+>-free solution in rat alveolar type II cells : Ca^<2+> regulation of Na^+-H^+ exchange.2005

    • Author(s)
      Murao H, Yoshida H, Nakahari T.他
    • Journal Title

      Experimental Physiology 90.2

      Pages: 203-213

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of ACh-stimulated exocytosis by NSAIDs in guinea pig antral mucous cells : autocrine regulation of mucin secretion by PGE22005

    • Author(s)
      Shimamoto C, Fujiwara S, Kato M, Ito S, Katsu K, Mori H, Nakahari T
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol. 288

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cell shrinkage evoked by Ca2+-free solution in rat alveolar type II cells : Ca2+ regulation of Na+/H+ exchange2005

    • Author(s)
      Murao H, Shimizu A, Hosoi K, Iwagaki A, Min KY, Kishima G, Hanafusa T, Kubota T, Kato M, Yoshida H, Nakahari T
    • Journal Title

      Exp Physiol 90(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ATP regulation of ciliary heat frequency in rat tracheal and distal airway epithelium2005

    • Author(s)
      Hayashi T, Kawakami M, Sasaki S, Katsumata T, Mori H, Yoshida H, Nakahari T
    • Journal Title

      Exp Physiol 90(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] β2-adrenergic regulation of ciliary beat frequency in rat bronchiolar epithelium : potentiation by isosmotic cell shrinkage.2004

    • Author(s)
      Shiima-Kinoshita C, Min KY, Hanafusa T, Mori H, Nakahari T.
    • Journal Title

      Journal of Physiology 554.2

      Pages: 403-416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Delayed shrinkage triggered by the Na+-K+ pump in terbutaline-stimulated rat alveolar type II cells.2004

    • Author(s)
      Hosoi, K, Min KY, Iwagaki A, Murao H, Hanafusa T, Shimamoto C, Katsu K, Kato M, Fujiwara S, Nakahari T.
    • Journal Title

      Experimental Physiology 89.4

      Pages: 373-385

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypo-osmotic potentiation of acetylcholine-stimulated ciliary beat frequency through ATP release in rat tracheal ciliary cells.2004

    • Author(s)
      Kawakami M, Nagira T, Hayashi T, Shimamoto C, Kubota T, Mori H, Yoshida H, Nakahari T.
    • Journal Title

      Experimental Physiology 89.6

      Pages: 739-751

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] β2-adrenergic regulation of ciliary beat frequency in rat bronchiolar epithelium : potentiation by isosmotic cell shrinkage2004

    • Author(s)
      Shiima-Kinoshita C, Min KY, Hanafusa T, Mori H, Nakahari T
    • Journal Title

      J.Physiol. 554,2

      Pages: 403-416

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Delayed shrinkage triggered by the Na+-K+ pump in terbutaline-stimulated rat alveolar type II cells.2004

    • Author(s)
      Hosoi K, Min KY, Iwagaki A, Murao H, Hanafusa T, Shimamoto C, Katsu K, Kato M, Fujiwara S, Nakahari T.
    • Journal Title

      Exp Physiol 89,4

      Pages: 373-385

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hypo-osmotic potentiation of acetylcholine-stimulated ciliary beat frequency through ATP release in rat tracheal ciliary cells.2004

    • Author(s)
      Kawakami M, Nagira T, Hayashi T, Shimamoto C, Kubota T, Mori H, Yoshida H, Nakahari T.
    • Journal Title

      Exp Physiol 89,6

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Maintenance of olfactory neurogenesis requires HSFI, a major heat shock transcription factor in mice.

    • Author(s)
      Takaki E, Fujimoto M, Sugahara K, Nakahari T, Yonemura S, Tanaka Y, Hayashida N, Inouye S, Takemoto T, Yamashita H, Nakai A.
    • Journal Title

      Journal of Biological Chemistry (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cyclic GMP modulation of Ach-stimulated exocytosis in guinea pig antral mucous cells

    • Author(s)
      Saad AH, Shimamoto C, Nakahari T, Fujiwara S, Katus K, Marunaka Y
    • Journal Title

      American Journal of Physiology Gastrointestinal Liver Physiology (in press)

    • NAID

      130005448316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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