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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)
大野 雅二  東京大学, 薬学部, 教授 (00111550)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 1991: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1990: ¥8,700,000 (Direct Cost: ¥8,700,000)
Keywordsplatelet-activating factor / PAF receptor / PAF antagonist / leukocytes / eosinophils / asthma / mast cells / PAF antibody / 血小板活性化因子 / アセチルトランスフェラ-ゼ / PAFアンダゴニスト / ラジオイムノアッセイ / ホスホリパ-ゼ / リゾPAF / ノ-アルケニルーGPE
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.

Report

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

    (26 results)

All Other

All Publications (26 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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugiura,T.,et al.: "Regulation of biosynthesis of platelet-activating factor in alveolar macrophages." Lipids. 26. 974-978 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ojima-Uchiyama,A.,et al.: "Production of platelet-activating factor by human normodense and hypodense eosinophils" Lipids. 26. 1200-1203 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Karasawa,K.,et al.: "Antibodies to synthetic platelet-activating factor (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) analogues with substituents." J.Biochem.110. 683-687 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hayashi,H.,et al.: "Biological response of guinea pig macrophages to platelet-activating factor" Lipids. 26. 1193-1199 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kudo,i.,et al.: "Guinea pig bone marrow cells treated with platelet-activating factor generate factor(s) which affects their DNA synthesis" Lipids. 26. 1065-1070 (1991)

    • Related Report
      1991 Annual Research Report
  • [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)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sugiura,T.,et al.: "PAF Receptor:Signal Mechanism and Molecular Biology" (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takayuki Sugiura et al.: "Ether lysophospholipidーinduced production of plateletーactivating factor in human polymorphonuclear leukocytes" Biochimica et Biophysica Acta. 1047. 223-232 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ken Karasawa et al: "Radioimmunoassay for Plateletーactivating Factor" Lipids. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ken Karasawa et al: "Specific Binding of Antibodies to Plateletーactivating Factor(PAF) as Demonstrated by ThinーLayer Chromatography/Immunostaining" Lipids. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Mori et al: "Extracellular phospholipase A_2 detected at inflamed sites in rats does not originate from platelets" Agents and Actions. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Murakami et al: "Exacerbatation of rat adjuvant arthritis by intradermal injection of purified mammalian 14ーkD_a phos pholipase A_2" FEBS Letter. 268. 113-116 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Suwa et al: "Proteinaceous in hibition of phospholipase A_2 purified from inflammatory sites in rats" Proceedings of the National Academy of Sciences of the United States of America. 87. 2395-2399 (1990)

    • Related Report
      1990 Annual Research Report

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

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