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Therapy for allergic diseases by a histamine degrading enzyme

Research Project

Project/Area Number 04670457
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionTohoku University

Principal Investigator

SEKIZAWA Kiyohisa  Tohoku University School of Medicine, Instructor, 医学部・附属病院, 助手 (50171335)

Co-Investigator(Kenkyū-buntansha) TEZUKA Mitsuhiko  Tohoku University School of Medicine, Instructor, 医学部・附属病院, 助手 (70227502)
FUKUSHIMA Takeyasu  Tohoku University School of Medicine, Instructor, 医学部・附属病院, 助手 (30218911)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHistamine N-methyltransferase / Histamine / Airway epighelium / Viral infection / Bronchial asthma / Vascular permeability / Submucosal edema / Allergic reaction / ウィルス感染
Research Abstract

1) We showed that histamine-N-methyltransferase is a principal enzyme responsible for histamine degradation in airways.
2) Histamine-N-methyltransferase (HMT) activities exist in the entire airway including the nasal mucosa in guinea pigs and humans.
3) HMTmRNA detected by in situ hybridization localized in the airway epithelium and endothelium.
4) HMT inhibitor SKF 91488 potentiated histamine- and antigen-induced bronchoconstriction and plasma extravasation in guinea pigs and did histamine-induced bronchoconstriction in humans.
5) Viral respiratory infection by Sendai virus caused bronchial hyperresponsiveness to histamine and decreased HMT activities in the entire airway.
6) The cDNA clone of human HMT was isolated from a cDNA library of human kidney. Human HMT consists of 292 amino acid residues (Mr 33,279).
7) Results indicate an important role of HMT in allergic diseases and cloning of human HMT may have clinical implications for therapy and understanding of pathophysiology in bronchial asthma and allergic rhinitis.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 大類 孝: "Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine" Journal of Pharmacology and Experimental Therapeutics. 261. 1268-1272 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 関沢 清久: "Histamine-N-methyltransferase modulates histamine- and antigen-induced bron choconstriction in guinea pigs in vivo" American Review of Respiratory Disease. 147. 92-96 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 中沢 秀喜: "Viral respiratory infection causes airway hyperrespunsiveness and decreases histamine N-methyltransferase activity in guinea pigs" American Journal of Respiratory and Critical Care Medicine. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 山内 広平: "Cloning of the cDNA encoding histamine N-methyl-transferase-a critical enzyme in histamine metabolism in the airway" American Journal of Physiology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 関沢 清久: "Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs" Journal of Allergy and Clinical Immunology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takashi Ohrui: "Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine" Journal of Pharmacology and Experimental Therapeutics. 261. 1268-1272 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kiyohisa Sekizawa: "Histamine-N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo" American Review of Respiratory Diseas. 147. 92-96 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kohei Yamauchi: "Cloning of the cDNA encoding histamine N-methyltransferase-a critical enzuyme in histamine metabolism in the airway-" American Journal of Physiology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hideki Nakazawa: "Viral respiratory infection causes airway hyperresponsiveness and decreases histamine N-methyltransferase activity in quinea pigs" American Journal of Respiratory and Critical Care Medicine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kiyohisa Sekizawa: "Histamene N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs" Journal of Allergy and Clinical Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 大類孝: "Histamine N-methyltrans ferase control the contractile response of guinea pig trachea to hiotamine" Journal of Pharmacology and Experimental Therapeutics. 261. 1268-1272 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 関沢清久: "Histamine -N-methyltransferase modulates his tamine- and antigen-induced bronchocomstriction in guineapigs in vivo." American Review of Respiratory Disease. 147. 92-96 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 中沢秀喜: "Viral respiratory infection causes airway hyperresponsiveness and decreases his to mine N-methyltransferase activity in guinea pigs" American Journal of Respiratory and Critical care Medicine. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 関沢清久: "Histamine N-methyl transferase inhibitor potentiates his tamine- and antigen-inducod airway micro vaocular leakage in guinea pigs" Journal of Allergy and Clinical Immunology. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 大類 孝: "Histamine N-methyltransferase control the contraitile response of guinea pig trachea to hiotamine" Journal of Pharmarology and Experimental The rapeutics. 261. 1268-1272 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 関沢 清久: "Histamine-N-methyltransferase modulates histamine and antigen-induced bronchoconstriction in guinea pigs in vivo" American Review of Respiratory Disease.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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