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The role of chemical mediators released from airway epithelial cells on airway contraction

Research Project

Project/Area Number 02454240
Research Category

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

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionUniversity of Tsukuba

Principal Investigator

HASEGAWA Shizuo  Institute of Clinical Medicine, University of Tsukuba, Professor, 臨床医学系, 教授 (90009481)

Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsEndothelin / Airway epithelium / Airway relaxation / Arachidonic asid / 遊離機構 / エンドセリン(ET)ー1 / モルモット / 経気道的投与 / 気道収縮 / エンケファリナ-ゼによる分解 / アナフィラキシ-反応後 / 気道平滑筋弛緩 / リポキシゲ-ゼ系アラキドン酸代謝産物
Research Abstract

Endothelin (ET), which is released from airway epithelial cells, elicits a potent bronchoconstriction, suggesting that ET plays an important role in regulating airway smooth muscle tone. Although airway epithelial cells can release ET, few study has been reported about the mechanism of ET release from epithelial cells. We, thus, studied the effect of chemical mediators on the synthesis of ET by cultured tracheal epithelial cells of the guineapig. Inflammatory mediators, such as histamine, prostaglandin F_<2*>, Platelet - activating factor (PAF), and bradyldnin had no effect on ET release, whereas prostaglandin E_2 and calcitonin gene related peptide (CGRP) stimulated the ET release from epithelial cells. Most cytokines including IL-1, IL-2, TNF, TGF-beta, upregulated the ET release and cordcosteroid downregulated one. These results lead us to the hypothesis that the release of ET from airway epithelial cells might increase under inflammation or immune response. Therefore, we are now investigating the effect of inflammatory cells on the ET synthesis by airway epithelial cells.
Previously, we reported the ET-induced airway smooth muscle relaxation after an an anaphylactic reaction in vitro. We determined the characteristics of this relaxation. The airway relaxation was elicited by ET-1 and ET-2, but not by ET-3. Epithelial removal increased and lipoxygenase inhibitors decreased this relaxation response. These results suggest that ET causes the airway smooth muscle relaxation via ET_A receptor and this response might be mediated by one of lipoxygenase products.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 早乙女 幹朗: "モルモット気管平滑筋におけるエンドセリンー1誘発弛緩性反応ーアナフィラキシ-反応後の気管切片を用いての検討ー" アレルギ-. 40(11). 1377-1383 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 渡辺 東: "Increased plasma level of endothelinー1 during asthmatic attack" Advances in Asthmology. 1990. 479-482 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 野村 明広: "Multiple mechanisms of bronchoconstrictive responses to endothelinー1" J.Cardiovasc.Pharmacol.17(Suppl.7). S213-S215 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 内田 義之: "Endothelinー1ーinduced relaxation of guinea pig trachealis muscles" J.Cardiovasc.Pharmacol.17(Suppl.7). S210-S212 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 野村 明広: "気道上皮と気道収縮ーエンドセリンー" 呼吸. 10(8). 940-945 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 二宮 浩樹: "Endotoxin stimulates endothelin release from cultured epithelial cells of guineaーpig trachea" Eur.J.Pharmacol.203. 299-302 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Saotome, S. Hasegawa et al.: "Endothelin-1 induced relaxation of guinea pig trachea after an anaphylactic reaction" Arerugi. 40(11). 1377-1383 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] A. Watanabe, S. Hasegawa et al.,: "increased plasma level of endothelin-1 during asthmatic attack" Advances in Asthmology. 479-482 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] A. Nomura, S. Hasegawa et al: "Multiple mechanisms of bronchoconstrictive responses to endothelin-1" J. Cardiovasc. Pharmacol. 17(Suppl. 7). S213-S215 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Uchida, S. Hasegawa et al.: "Endothelin-1-induced relaxation of guinea-pig trachealis muscles." J. Cardiovasc. Pharmacol. 17(Suppl. 7). S210-S212 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Ninomiya, S. Hasegawa et al.: "Endotoxin stimulates endothelin release from cultured epithelial cells of guinea-pig trachea." Eur. J. Phamacol. 203. 299-302 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 早乙女 幹朗: "モルモット気管平滑筋におけるエンドセリンー1誘発弛緩性反応ーアナフィラキシ-反応後の気管切片を用いての検討ー" アレルギ-. 40(11). 1377-1383 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 渡辺 東: "Increased plasma level of endothelinー1 during asthmatic attack" Advances in Asthmology. 1990. 479-482 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 野村 明広: "Multiple mechanisms of bronchoconstrictive responses to endothelinー1" J.Cardiovasc.Pharmacol.17(Suppl.7). S213-S215 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 内田 義之: "Endothelinー1ーinduced relaxation of guinea pig trachealis muscles" J.Cardiovasc.Pharmacol.17(Suppl.7). S210-S212 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 野村 明広: "気道上皮と気道収縮ーエンドセリンー" 呼吸. 10(8). 940-945 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 二宮 浩樹: "Endotoxin stimulates endothelin release from cultured epithelial cells of guineaーpig trachea" Eur.J.Pharmacol.203. 299-302 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 野村 明広: "Endothelinとアレルギ-反応" 臨床免疫. 22(5). 666-671 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 内田義之: "エンドセリンと肺" 呼吸. 8(11). 1161-1164 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 野村明広: "Endothelin and Bronchial Asthma" The Lancet. II(8665). 747-748 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 内田義之: "Endothelin,a novel vasoconstrictor peptide,as potent bronchoconstrictor" Eur.J Pharmacol.154(2). 227-228 (1988)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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