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1991 Fiscal Year Final Research Report Summary

Healing of several PAF-derived diseases by newly disigned PAF antagonists

Research Project

Project/Area Number 02557093
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionFaculty of Pharmaceutical Sciences, Teikyo University

Principal Investigator

WAKU Keizo  Faculty of Pharmaceutical Sciences, Teikyo University, Professor, 薬学部, 教授 (90013854)

Co-Investigator(Kenkyū-buntansha) HIRAOKA Tetsuo  New Lead research Laboratories, Sankyo Co., Ltd., Head Chief, 活性物質研究所, 所長
KOBAYASHI Susumu  Faculty of Pharmaceutical Sciences, University of Tokyo, Assistant Professor, 薬学部, 助教授 (70101102)
INOUE Keizo  Faculty of Pharmaceutical Sciences, University of Tokyo, Professor, 薬学部, 教授 (30072937)
NOJIMA Shosichi  Faculty of Pharmaceutical Sciences, Teikyo University, Professor, 薬学部, 教授 (70090470)
Project Period (FY) 1990 – 1991
Keywordsplatelet-activating factor / PAF receptor / PAF antagonist / leukocytes / eosinophils / asthma / mast cells / PAF antibody
Research Abstract

1. Waku, the organizer of this project, studied the production and release of Platelet Activa% Factor(PAF)in the human eosinophils. The A 23187-activated hypodense eosinophils could produce PAF 3-4 times more strongly than the normodence eosinophils and could easily release PAF from the eosinophil cells. The production of superoxide anion(O_2)by the human eosinophils is also studied in comparison with that of human neutrophils. The human eosinophds could produce(O_2)4-5 times more strongly than the human neutrophits on the stimulation by PAF and these results suggest du the damage of lung celts by eosinophils may be due to the strong production of this superoxide anion by the stimulation of PAF.
2. Nojima has prepared the PAF antibody by injecting dimethylcarbamoyl-CPGPC to rabbit. This antibody strongly suppressed the platelet coagulation of mbbit and may be useful for protecting animals from the anapbylactic shock caused by PAF.
3. Inoue has demo d that the decrease of number of mouse neutrophils by X-ray irradiation was protected by injecdag PAF agonist to the mouse. These results show the role of PAF for the proliferation of neutrophffs in mouse bone marrow.
4. Kobayashi has newly designed the PAF antagonist having bicyclo compounds, which is 10 times more effective as an PAF antgonist than the standard PAF antagonist, CV-3988. It is hoped that these newly designed PAF antagonist could be very effective to the PAF receptor of eosinophils.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Sugiura,T.,et al.: "Ether-lysophospholipid-induced production of platelet-activating factor in human polymorphonuclear leukocytes" Biochim.Biophys.Acta. 1047. 223-232 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suwa,Y.,et al.: "Proteinaceous inhibition of phospholipase A_2 purified from inflammatory sites in rats" Proc.Nat1.Acad.Sci.USA. 87. 2395-2399 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ojima-Uchiyama,A.,et al.: "Production of platelet-activating factor by human normodense and hypodense eosinophils" Lipids. 26. 1200-1203 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] karasawa,K.,et al.: "Antibodies to synthetic platelet-activating factor analogues with substituents at the sn-2 position" J.Biochem.110. 683-687 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kudo,I.,et al.: "Guinea pig bone marrow cells treated with platelet-activating factor generate factor(s) which asffects their DNA synthesis and microbicidal activity" Lipids. 26. 1065-1070 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi.S.,et al.: "Development of tetrahydrofuran chiral synthons by enzymatic approach:Improved synthesis of a strong agonist of platelet-activating factor" Tetrahedron Lett.(1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugiura,T.et al.: "PAF Receptor:Signal Mechanism and Molecular Biology" (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugiura, T., et al.: "Ether-lysophospholiped-induced production of platelet-activating factor in human polymorphonuclear leukocytes." Biochim. Biophys. Acta. 1047. 223-232 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suwa, Y., et al.: "Proteinaceous inhibition of phospholipase A_2 purified from inflammatory sites in rats." Proc. Natl. Acad. Sci. USA. 87. 2395-2399 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ojima-Uchiyama, A., et al.: "Production of platelet-activating factor by human normodense and hypodense neutrophils." Lipids. 26. 1200-1203 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Karasawa, K., et al.: "Antibodies to synthetic platelet-activating factor analogues with substituents at the sn-2 position." J. Biochem.110. 683-687 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kudo, I., et al.: "Guinea pig bone marrow cells treated with platelet-activatin factor generate factor (s) which affects their DNA synthesis and microbicidal activity." Lipids. 26. 1065-1070 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, S., et al.: "Development of tetrahydrofuran chiral synthons by enzymatic approach : Improved synthesis of a strong agonist of platelet-activating factor." Tetrahedron Lett.(1992)

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

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Published: 1993-03-16  

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