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2001 Fiscal Year Final Research Report Summary

Molecular mechanisms underlying age-dependent decrease of water transport in salivary glands and the investigation of the drug in xerostomia

Research Project

Project/Area Number 11557137
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional basic dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

ISHIKAWA Yasuko  The University of Tokushima, Sch. of Dentistry, Associate Professor, 歯学部, 助教授 (40144985)

Co-Investigator(Kenkyū-buntansha) EGUCHI Takafumi  The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (90263847)
MARCHLIK Wojciech  The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (00335803)
ISHIDA Hajime  The University of Tokushima, Sch. of Dentistry, Professor, 歯学部, 助教授 (70028364)
IMAI Yasuo  The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (30271068)
SKOWRONSKI Mariusz  The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (00294702)
Project Period (FY) 1999 – 2001
KeywordsWater channel / Aquaporin-5 / cis-2-methylspiro-(1,3-oxathiolane-5, 3')-quinuclidine / Aging / Salivary glands / [ Ca^<2+> ]i / M3-Muscarinic receptor / Apical plasma membrane
Research Abstract

The stimulatory effect of acetylcholine, but not that of epinephrine, on the abundance of aquaporin-5 in the apical plasma membrane (APM) of parotid acinar cells was markedly reduced in tissue from senescent rats relative to that in tissue from young adult animals. In this study, we looked for the drug which persistent increase in the amount AQP5 in the APM of-parotid glands of senescent rats.
cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine induced a marked increase of AQP5 in the APM of parotid tissues in a dose-dependent manner with an EC_<50> value of 14.2 ± 2.3 nM. cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine- and pilocarpine-induced increase in the amount of AQP5 in the APM was maximal at 10 and 3 min, respectively, and persisted for longer than 30 min. This increase was inhibited by pF-HHSiD, U73122, dantrolene or TMB-8, but not by GF 109203X. In the presence of extracellular CaCl_2, cis-2-methylspiro- (1,3- oxathiolane-5,3')-quinuclidine induced marked and persistent oscillations in [ Ca^<2+> ]i in isolated acinar cells. These results suggest that cis-2-methylspiro-(1,3- oxathiolane-5,3')-quinuclidine acts at M_3 receptors to induce a persistent increase in the amount of AQP5 in APM of parotid acini, and that this effect is mediated by the release of Ca^<2+> from intracellular stores through both inositol 1,4,5-trisphosphate and ryanodine receptors.
The cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine induced a persistent increase in the amount of aquaporin-5 in the apical plasma membrane that was similar for parotid tissue from young adult and senescent rats, suggesting that this drug prove effective for treatment of age-related xerostomia.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Yasuko Ishikawa: "α1-Adrenoceptor-induced trafficking of aquaporine-5 to the apical plasma membrane of rat parotid cells"Biochemical and Biophysical Research Communications. 265. 94-100 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mariusz T.Skowronski: "Enhancement by epinephrine of benzylpenicillin transpor in rat small intestine"The Journal of Pharmacology and Exoer imental Therapeutics. 293. 128-135 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuko Ishikawa: "Aquaporine water channel in salivary glands"The Japanese Journal of Pharmacology. 83. 95-101 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuko Ishikawa: "Persistent increase in the amount of aquaporin-5 in the apical plasma membreneof rat parotid・・・・・"FEBS Letters. 477. 253-257 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuko Ishikawa: "Activation of endogenous nitric synthase coupled with methacholine-induced exocytosis in rat・・・・・"The Journal of Pharmacology and Experimental therapeutics. 301(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuko Ishikawa: "The muscarinic acetycholine receptor-stimulated increase in AQP5 levels in the apical plasma・・・・・"Molecular Pharmacology. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuko Ishikawa: "Molecular Biology and Physiology of water and Solute Transport(ed.by S.Hohmann)"Kluwer Academic/Plenum Publishers. 451 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishikawa,Yasuko: "α1-Adrenooeptorinduoed trafficking of aquaporine-5 to the apical plasma membrane of rat parotid cells"Biochemical and Biophysical Research Communications. 265. 94-100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mariusz,Skowronski: "Enhancement by epinephrine of benzylpenicillin transport in rat small intestine"The Journal of Pharmacology and Experimental Therapeutics. 293. 128-135 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa,Yasuko: "Aquaporine water channel in salivary glands"The Japanese Journal of Pharmacology. 83. 95-101 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa,Yasuko: "Persistent increase in the amount of aquaporin-5 in the apical plasma membrane of rat parotid atinar cells induced by the muscarinic receptor agonist SNI-2011"FEBS Letters. 477. 253-257 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa,Yasuko: "Activation of endogenous nitric synthase coupled with methacholine-induced exocytosis in rat parotid acinar cells"The Journal of Pharmacology and Experimental Therapeutics. 301. 1-9 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa,Yasuko: "The muscarinic acetylcholine receptor-stimulated increase in AQP5 levels in the apical plasma membrane in rat parotid acinar cells coupled with activation of NO/cGMP signal transduction"Molecular Pharmacology. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa,Yasuko: "Elsevier Sciene BV"Contral and Diseases of Sodium Dependent Transport Proteins and Ion Channels )ed. by Y. Suketa). 440 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa,Yasuko: "Kluwer Academic Plenum Publishers"Molecular Biology and Physiology of Water and Solute Transport )ed. by S. Hohmann). 451 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishida,Hajime: "Elisevier Science BV"Histamine Research in the New Millennium. 521 (2001)

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

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Published: 2003-09-17  

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