Fundamental research for an inhalational therapy using hyposmotic solution to stimulate airway ciliary motility
| Project/Area Number |
16590169
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
NAKAHARI Takashi Osaka Medical College, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20189020)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | airway 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 |
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| 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.
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Report
(3 results)
Research Products
(22 results)
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[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.
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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
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[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
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Journal Title
Related Report
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[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.
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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
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[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.
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Journal Title
Exp Physiol 89,4
Pages: 373-385
Related Report
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[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.
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Journal Title
Journal of Biological Chemistry (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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