1989 Fiscal Year Final Research Report Summary
Development of new drugs affecting PAF action by interacting to receptors and metabolizing enzymes.
| Project/Area Number |
63870099
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, Teikyo University |
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Principal Investigator |
NOJIMA Shoshichi Teikyo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70090470)
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| Co-Investigator(Kenkyū-buntansha) |
WAKU Keizo Teikyo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90013854)
HIRAOKA Tethuo Sankyo Co., LTD.New Read Research Laboratories, Head, 所長
OHNO Masaji Tokyo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00111550)
INOUE Keizo Tokyo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30072937)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Platelet-Activating Factor / PAF antibodies / PAF / Radioimmunoassay / PAF antagonists / Anti-PAF drugs / PAF metabolizing enzymes |
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| Research Abstract |
PAF has been suggested to play a pathophysiological role in asthma and inflammatory diseases. The aim of our investigation is a development of new drugs affecting the action of PAF by interacting to various factors such as receptors, metabolizing enzymes and carrier proteins. The following results were obtained in the present study. We developed a sensitive (50 pg, 0.1 pmol) and simple immunoassay method for PAF utilizing PAF antibodies, which were prepared by immunizing rabbits with a conjugate of synthetic PAF analog and bovine serum albumin. Natural phospholipids such as lecithin and lysoPAF do not exhibit detectable cross-reactivities (<O.025 %). This radioimmunoassay was applied for the analysis of PAF formation after stimulating alveolar macrophages. Accuracy and linearity of the radioimmunoassay are satisfactory by using solvent extraction and HPLC. The amount of PAF estimated by radioimmunoassay was comparable to the results already obtained by bioassay. In addition, we examined the regulation of PAF metabolism to the target cells of PAF action. Degradation and cellular translocation of PAF were decreased in the ATP-depleted platelets, suggesting that there are carriers of PAF which are separable from PAF receptors in these cells. Furthermore, we studied synthesis of PAF in human peripheral neutrophils and eosinophils which are involved in allergic diseases. PAF production by these cells is increased in the pathological states. Finally, we designed and synthesized a novel compound, 7-oxabicyclo[2.2.1]heptane derivative based on structure-activity relationship and it was shown to have a potent PAF antagonist activity. We are now underway to investigate its therapeutic values on several diseases.
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[Publications] K.Karasawa,N.Satoh,T.Hongo,M.Setaka,H.Mowri,T.Takano,S.Hashimoto,S.IKegami,K.Fujita,M.Ohno and S.Nojima: "Trends in pharmacological Research Platelet-Activating Factor(PAF)in Japan" Ishiyaku EuroAmerica,Inc., 208 (1988)
Description
「研究成果報告書概要(和文)」より
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