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Analyses of induction mechanisms underlying nasal blockage and nasal hyperresponsiveness using an experimental model of allergic rhinitis

Research Project

Project/Area Number 15590080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

KOHNO Shigekatsu  Kyoto Pharmaceutical University, Faculty of Pharmacy, Professor, 薬学部, 教授 (50082988)

Co-Investigator(Kenkyū-buntansha) NABE Takeshi  Kyoto Pharmaceutical University, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (40228078)
YASUI Hiroyuki  Kyoto Pharmaceutical University, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (20278443)
TAKENAKA Hiroshi  Osaka Medical College, Faculty of Medicine, Professor, 医学部, 教授 (40137162)
桜井 弘  京都薬科大学, 代謝分析学教室, 教授 (30065916)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsAllergic rhinitis / Pollenosis / Nasal blockage / Nasal hyperresponsiveness / Arachidonic acid metabolites / Kinins / Immunotherapy / Anti-allergic drugs / 減感作療法 / くしゃみ / IgE / ロイコトリエン / トロンボキサン / 遅発性反応 / ヒスタミン
Research Abstract

We have developed an experimental allergic rhinitis model by repetitive inhalation challenges with Japanese cedar pollen in sensitized guinea pigs. In this model, sneezing is induced immediately after challenges, and biphasic nasal blockage were also induced with peaks at 1-2 and 4-6 h after challenges. Furthermore, nasal hyperresponsiveness to non-specific stimuli was developed 10 h-2 days after challenges. Among these symptoms, nasal blockage and nasal hyperresponsiveness are serious symptoms for patient's daily life. Medicines to relieve these signs are only corticosteroids, which shows various side effects.
In this study, in order to analyze induction mechanisms underlying nasal blockage and nasal hyperresponsiveness, roles of several mediators are evaluated. In addition, we assessed effect of oral immunotherapy on inductions of these symptoms as a fundamental therapeutic strategy. Results obtained are as follows :
1.It was strongly suggested that the nasal hyperresponsiveness is ind … More uced by kinins such as bradykinin that are produced immediately after antigen challenge through activation of B_1 and B_2 receptors, which have been newly and constitutively expressed on the nasal mucosa.
2.Arachidonic acid metabolites, cysteinyl leukotrienes and thromboxane A_2 are involved in the induction of the antigen-induced late phase nasal blockage through synergistically acting on the nasal mucosa.
3.When the pollen extract was orally administered during the challenging period, inductions of nasal blockage and nasal hyperresponsiveness were strongly suppressed.
In conclusion, arachidonic acid metabolites described above and kinins are suggested to play important roles in inductions of nasal blockage and nasal hyperresponsiveness, respectively. Especially, because antagonists against kinin receptors have not been clinically used, this class of compounds could be new therapeutic drugs for allergic rhinitis. In addition, we hope that our present result showing the effectiveness of the oral immunotherapy could stimulate further clinical examinations evaluating effects of the immunotherapy on allergic rhinitis symptoms. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (14 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (2 results)

  • [Journal Article] Effect of oral immunotherapy on nasal blockage in experimental allergic rhininitis2005

    • Author(s)
      Takeshi Nabe
    • Journal Title

      Journal of Pharmacological Sciences 98・4

      Pages: 380-387

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] モルモットアレルギー性鼻炎モデルを用いた鼻閉の発症機序の薬理学的解析2005

    • Author(s)
      奈邉 健
    • Journal Title

      日本薬理学雑誌 125・5

      Pages: 271-277

    • NAID

      10016428949

    • 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] Effect of oral immunotherapy on nasal blockage in experimental allergic rhinitis2005

    • Author(s)
      Takeshi Nabe
    • Journal Title

      Journal of Pharmacological Sciences 98-4

      Pages: 380-387

    • NAID

      10025729519

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pharmacological analyses of mechanisms underlying nasal blockage using a guinea-pig model of allergic rhinitis2005

    • Author(s)
      Takeshi Nabe
    • Journal Title

      Nippon Yakurigaku Zasshi 125-5

      Pages: 271-277

    • NAID

      10016428949

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of oral immunotherapy on nasal blockage in experimental allergic rhinitis2005

    • Author(s)
      Takeshi Nabe
    • Journal Title

      Journal of Pharmacological Sciences 98・4

      Pages: 380-387

    • NAID

      10025729519

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Synergism between cysteinyl leukotrienes and thromboxane A_2 to induce allergic late phase nasal blockage in guinea pigs2004

    • Author(s)
      Yasutomo Nakanishi
    • Journal Title

      Prostaglandins & Other Lipid Mediators 74・1-4

      Pages: 125-137

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Synergism between cysteinyl leukotrienes and thromboxane A_2 to induce allergic late phase nasal blockage in guinea pigs2004

    • Author(s)
      Yasutomo Nakanishi
    • Journal Title

      Prostaglandins & Other Lipid Mediators 74-1-4

      Pages: 125-137

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Synergism between crysteinyl leukotrienes and thromboxane A_2 to induce allergic late phase nasal blockage in guinea pigs2004

    • Author(s)
      Yasutomo Nakanishi
    • Journal Title

      Phostaglandins & Other Lipid Mediators 74

      Pages: 125-137

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs2003

    • Author(s)
      Shingo Sugahara
    • Journal Title

      European Journal of Pharmacology 476・3

      Pages: 229-237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Acquired nasal hyperresponsiveness aggravates antigen-induced rhinitis in the guinea pig2003

    • Author(s)
      Nobuaki Mizutani
    • Journal Title

      Journal of Pharmacological Sciences 93・4

      Pages: 437-445

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs2003

    • Author(s)
      Shingo Sugahara
    • Journal Title

      European Journal of Pharmacology 476-3

      Pages: 229-237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Acquired nasal hyperresponsiveness aggravates antigen-induced rhinitis in the guinea pig2003

    • Author(s)
      Nobuaki Mizutani
    • Journal Title

      Journal of Pharmacological Sciences 93-4

      Pages: 437-445

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Shingo Sugahara: "Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs"European Journal of Pharmacology. 476. 229-237 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nobuaki Mizutani: "Acquired nasal hyperresponsiveness aggravates antigen-induced rhinitis in the guinea pig."Journal of Pharmacological Sciences. 93. 437-445 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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