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1995 Fiscal Year Final Research Report Summary

Pharmacological studies on the active factors derived from airway epithelial cells.

Research Project

Project/Area Number 06454162
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKyushu University

Principal Investigator

ITO Yushi  Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (80037506)

Co-Investigator(Kenkyū-buntansha) HIRATA Masato  Kyushu University, Faculty of Dentistry, Assistant Professo, 歯学部, 助教授 (60136471)
INOUE Ryuji  Kyushu University, Faculty of Medicine, Assistant Professo, 医学部, 助教授 (30232573)
Project Period (FY) 1994 – 1995
KeywordsAirway epithelial cell / Hyperpolarizing factor / Airway smooth muscle / Resting membrane potential / Arachidonic acid / Prostaglandins / Peptide / Airway hyper responsiveness
Research Abstract

Airway epithelial cells do not simply act as diffusion barriers against airway stimulating substances such as toxic gases or antigens, but play an important role in regulation of the airway muscle tone by rekeasing multiple active factors. Namely, airway epitelial cells release more than two factors, one of which inhibits excitatory neuro-effector tranamission and an other which modulates the resting membrane potential of the airway smooth muscle cells. To identify these factors we cultured airway epithelial cells and used the cultuured supernatants. Cultured supernatants completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulation and suppressed the excitatory junction potentials. Cultured epithelial cells produce prostaglandins, and exogenously applied PGE_2 inhibits excitatory neuro-effector transmission presynaptically in the dog trachea and bronchioles. Therefore we radioimmunoassayd the amounts of PGE_2 in the super … More natants, which ranged between 3.1-23.8ng/ml. A high concentration of PGE_2 in the supernatant was associated with aboliton of the twitch contraction. Indomethacin, which suppresses the synthesis of PGE_2 in the suprenatants, prevented the inhibitory effect of supernatants on the twitch contractions and excitatoty junction potentials. Thus we concluded that one of the factors which is released from the airway epithelial cells and inhibits excitatory neuro-effector transmission is PGE_2. In an attempt to identify the epithelium derived hyperpolarizing factor (EpDHF) , we freeze-dried the supernatants and then applied them to Gel-filtration chromatograohy on Sephacryl S-100HR and then high-perfoamace liquid chromatofraphy on a c_<18> reversed-phase column. Hyperpolarization assay of the chromatographic fractions showed that active factors eluted in peaks coincided with low molecular weights (10-20 KD). Enzymatic treatment with proteolytic enzymes of the HPLC-purified active fraction resuletd in the abolition of hyperpolarizing activity.The results suggest that the active factor (EpDHF) 1 that was present in the cultured epithelial supenatants was a peptide in nature. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] M. Matsumoto: "Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscle." Am. J. Respir. Cell Mol. Biol.10. 322-330 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N. A. Adbullah: "Contraction and depolarization induced by fetal bovine serum in airway smooth muscle." Am. J. Physiol.266. L528-L535 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊東祐之: "気道上皮細胞による気道平滑筋の制御" 日薬理誌. 103. 141-150 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] L. Jing: "Role of nitric oxide in non-adrenergic, non-cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway." J. Physiol.483. 225-237 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N. Takahashi: "Regional difference in the distribution of L-NAME-sensitive and-insensitive NANC relaxations in cat airway." J. Physiol.488. 709-720 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Tanaka: "The possible role of nitric oxide on relaxations and excitatory neuro-effector transmission in the cat airway." J. Physiol.in press (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Ito: "Airway Smooth Muscle Biochemical Control of Contraction and Relaxation, eds. by D. Raebum & M. A. Giembryc" Birkhauser Verlag, pp153-186 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Matsumoto: "Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smootn muscle." Am.J.Respir.Cell Mol.Biol.10. 322-330 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.A.Adullah: "Contraction and depolarization induced by fetalbovine serum in airway smooth muscle." Am.J.Physiol.266. L528-L535 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] L.Jing: "Role of nitric oxide in non-adrenergic, non-cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway." J.Physiol.483. 225-237 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Takahashi: "Regional difference in the distribution of L-NAME-sensitive and -insensitive NANC relaxations in cat airway." J.Physiol.488. 709-720 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Tanaka: "The possible role of nitric oxide on relazations and excitatory neuro-effector transmission in the cat airway." J.Physiol. (in press). (1996)

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

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Published: 1997-03-04  

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