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Mechanism underlying streptozotocin-induced xerostomia and curative drug

Research Project

Project/Area Number 13470393
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) YUAN Zhenfang  The University of Tokushima, School of Dentistry, Assistant Researcher, 歯学部, 助手 (80346600)
IIDA Hirokazu  The University of Tokushima, School of Dentistry, Assistant Researcher, 歯学部, 助手 (10335797)
マーリック ウォーテック・ダニエル  徳島大学, 歯学部, 助手 (00335803)
石田 甫  徳島大学, 歯学部, 教授 (70028364)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥9,400,000 (Direct Cost: ¥9,400,000)
KeywordsWater channel / Aquaporin-5 / Salivary glands / Diabetes / Xerostomia / Lipid rafts / Apical membrane / Cevimeline / SNI-2011 / アクアポリン-5 / アクアポリン-8 / M3ムスカリン受容体 / 唾液分泌不全 / チアゾリジン系薬物
Research Abstract

Parotid secretory response to the activation of M3-muscarinic acetylcholine receptors (mAChRs) is reduced in streptozotocin.-induced diabetic (STZ) rats. In this research eve investigated the mechanisms involved in the decreased secretory response in coupled with the alteration of the distribution of aquaporin-5 (AQP5) water channel. Parotid slices from Wister rats gived STZ were incubated with or without mAChR agonists or other agents. Cevimeline hydrochloride (SNI-2011) increased AQPS levels in apical plasma membrane by 3-fold in parotid glands in normal rats, but by 0.8-fold in those of STZ rats. SNI-2011 increases AQP5 levels in basolateral membrane in STZ rats. Although mRNA of AQP5 was increased, the amount of AQP5 in parotid homogenate or lipid rafts was decreased in STZ rats. Both the quantities and affinity of mAChRs were decreased, but the amount of Gq proteins were not changed in STZ rats compared with ncontrol rats. In conclusion, mAChR agonists did not induce the increase in the amount of AQP5 in the apical plasma membrane of parotid glands from STZ rats because of the ~~ defect of translocation of AQP5 from rafts to the apical plasma membrane

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Noriko Inoue, et al.: "Age-related decreases in the response of aquaporin-5 to acetylcholine in rat parotid glands."Journal of Dental Research. 82. 476-480 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhenfang Yuan, et al.: "Effect of SNI-2011 on amylase secretion from parotid tissue in rats and in neuronal nitric oxide synthase knockout mice."European Journal of Pharmacology. 464. 197-206 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 石川康子, 他: "セビメリン;アクアポリン(水チャネル)の細胞内移動により唾液分泌を促進するくすり"Molecular Medicine. 41. 500-507 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuko Ishikawa, et al.: "The defect of translocation of aquaporin-5 in rat parotid glands leads to xerostomia."Journal of Pharmacological Science. 94. 57 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhenfang Yuan, et al.: "The defect of translocation of aquaporin-5 in rat parotid glands of streptozotocin-induced diabetic rats."Journal of Pharmacological Science. 94. 75 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 石川康子, 他: "第5版 歯科薬理学"医歯薬出版株式会社. 550 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Noriko Inoue et al.: "Age-related decreases in tie response of aquaporin-5 to acetylcholine in rat parotid glands"Journal of Dental Reserch. 82. 476-480 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhenfang Yuan et al.: "Effect of SNI-2011 on amylase secretion from parotid tissue inrats and in neuronal nitric oxide synthase knockout mice"European Journal of Pharmacology. 464. 197-206 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuko Ishikawa et al.: "The defect of translocation in rat parotid glands leads to xerostomia"Journal of Pharmacological Science. 94. 57 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhenfang Yuan: "The defect of translocation of aquaporin-5 in rat parotid glands streptozotocin-induced diabetic rats"Journal of Pharmacological Science. 94. 75 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuko Ishikawa et al.: "Cevimeline ; A salivary stimulant that induces intracellular translocation of aquaporin"Molecular Medicine. 41. 500-506 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Noriko Inoue, et al.: "Age-related decreases in the response of aquaporin-5 to acetylcholine in rat parotid glands"Journal of Dental Research. 82. 476-480 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zhenfang Yuan, et al.: "Effect of SNI-2011 on amylase secretion from parotid tissue in rats and in neuronal nitric oxide synthase knockout mice"European Journal of Pharmacology. 464. 197-206 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 石川康子 他: "セビメリン;アクアポリン(水チャネル)の細胞内移動により唾液分泌を促進するくすり"Molecular Medicine. 41. 500-507 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuko Ishikawa, et al.: "The defect of translocation of aquaporin-5 in rat parotid glands leads to xerostomia"Journal of Pharmacological Science. 94. 57 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zhenfang Yuan, et al.: "The defect of translocation of aquaporin-5 in rat parotid glands of streptozotocin-induced diabetic rats"Journal of Pharmacological Science. 94. 75 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 石川康子 他: "第5版 歯科薬理学"医歯薬出版株式会社. 550 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuko Ishikawa: "The musucarinic acetylcholine receptor-stimulated increase in aluaporin-5 levels in the apical plasma membrane in rat parotid acinar cells is coupled with activation…"Molecular Pharmacology. 61・6. 1423-1434 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuko Ishikawa: "Activation of endogenous nitric oxide synthase coupled with metacholine-induced Exocytosis in rat parotid acinar cells"The Journal of Pharmacology and Experimental Therapeutics. 301・1. 355-363 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhenfang Yuan: "Effect of SNI-2011 on amylase secretion from parotid tissue in rats and in neuronal nitric oxide synthase knockout mice"European Journal of Pharmacology. 464・2-3. 197-206 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuko Ishikawa: "Activation of endogenous nitric oxide synthase coupled with methacholine-induced exocytosis in rat parotid acinar cells"J. Pharmacol. Exp. Ther.. Vol.301 No.1. 1-9 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuko Ishikawa: "Regulation of Gi2α phoshporylation controls isoprenaline-induced supersensitivity and desensitization of amylase secretion in rat parotid glands"9^<th> International Catecholamine Symposium. 44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuko Ishikawa: "Neurotransmitters regulate amount of AQP5 in apical membrane of parotid"Journal Dental Research. Vol.80. 600 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hajime ishida: "Phosphorylation/dephosphorylation of Gi regulates desensitization/supersensitivity in response to β2-adrenergic agonist"Journal Dental Research. Vol.80. 676 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noriko Inoue: "SNI-2011-induced persistent increase in the amount of AQp5 in APM"Journal Dental Research. Vol.80. 676 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 石川康子: "耳下腺のAQP5とAQP8の神経性調節"歯科基礎医学会雑誌. Vol.43, No.5. 551 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 石田甫: "コリン作動薬による耳下腺腺房細胞におけるNOとcGMPの生成とアミラーゼ分泌"歯科基礎医学会雑誌. Vol.43, No.5. 588 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 井上紀子: "糖尿病と唾液腺分泌機能の変化"歯科基礎医学会雑誌. Vol.43, No.5. 588 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 石川康子: "SNI-2011による持続性唾液分泌と水チャネルAQp5の連関性"日本唾液腺学会誌. 42. 39-42 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuko Ishikawa: "The activation of NO/cGMP signal transduction induces the increase in AQP5 levels in the apical plasma membrane in rat parotid glands"Japanese Journal of Pharmacology. Vol.81, Suppl.. 221 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirokazu Iida: "Activation of endogenous NOS coupled with methacholine(MCh)-induced amylase secretion exocytosis in rat parotid acinar cells"Japanese Journal of Pharmacology. Vol.81, Suppl.. 174 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hajime Ishida: "Regulation of phosphorylation status of Gi2α couples with β2-adrenergic agonist-induced desensitization and supersensitivity …"XIVth International Congress of Pharmacology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuko Ishikawa: "Activation of endogenous nitric oxide synthase coupled with methacholine-induced exocytosis in rat parotid acinar cells"XIVth International Congress of Pharmacology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuko Ishikawa: "The ACh-and pilocarpine-induced increase in AQP5 levels in the APM in rat paroptid acinar cells is coupled with activation of …"XIVth International Congress of Pharmacology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 石田甫: "「顎関節症入門」薬物療法 編著;森本俊文・松矢篤三・野首孝祠・小林義典"医歯薬出版株式会杜. 249 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuko Ishikawa: "「Molecular biology and physiology of water and solute transport」 Edited by Stefan"Kluwer Academic/Plenum Publishers, London, UK. 451 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hajime Ishida: "「Histamine Research in the New Millennium」 Edited by Takehiko Watanabe, Henk Timmerman and Kazuhiko Yanai"Elsevier Science Publishing Co, Amsterdam, The Netherlands. 521 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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