| Project/Area Number |
61870094
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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, University of Tokyo |
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Principal Investigator |
OHNO Masaji University of Tokyo, Professor, 薬学部, 教授 (00111550)
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| Co-Investigator(Kenkyū-buntansha) |
森 弘 帝国臓器(株), 常務取締役
SHIGENORU Koki University of Tokyo Associate Professor., 薬学部, 助教授 (50012654)
WAKU Keizo Teikyo University, Professor, 薬学部, 教授 (90013854)
INOUE Keizo University of Tokyo, Professor, 薬学部, 教授 (30072937)
NOJIMA Shoshichi Teikyo University, Professor, 薬学部, 教授 (70090470)
MORI Hiroshi Teikoku Hormone MFG. Co. Ltd., Managing Director
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1987: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1986: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | Platelet Activating Factor / 1(S)-Me-PAF / Phospholipase A_2 / Drug Design / Anti- hypertensive / Anti-coagulative / Anti-inflammative / PAF抗体 / phospholipase 【A_2】 / L-酒石酸 |
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| Research Abstract |
The characteristic features of this project include the following points; (1) the investigation of the basic fole of platelet activating factors (PAF) in the body through close cooperation of biochemists, pharmacologists, and organic chemists and; the construction of novel agents having anti-hypertensive, anticoagulative or anti-inflammative property based on PAF structures. The following results were obtained during the past two years (1986-1988).
(1) Various derivative were prepared by introducing various substituents at C-1 position of the glycerin backbone and submitted to the biological test (hypoten- sive effect in vitro and vivo and serotonine release) Lt was confirmed that only 1(S)-Me-PAF strongly reduces the blood pressure of rat and activates moderately platelet. Therefore, it is considered to be a selective agonist for the first time, and brought us to design a novel tetrahydrofuran derivative, a conformationally restricted model, which showed similar activity as PAF.
(2) The study of the substrate specificity of PAF-degradating enzymes from various sources was investigated by using PAF and the synthetic analogs. Tissue-originated acetylhydrolases deacetylated 1(S)-Me-PAF slightly faster than PAF, whereas plasma acetylhydrolase hydrolyzed PAF more effectively than 1(S)-Me-PAF.
(3) Absorption and deacetylation of 1(S)-Me-PAF at rat intestine were studied and it was shown that there were little differences in the absorption, but PAF was deacetylated more rapidly than 1(S)-Me-PAF.
(4) The biochemical study of the role of PAF first suggested that PAF may affect a class of guinea pig bone marurow cells through binding to PAF specific binding sites, resulting in activation and/or induction of differentiation of monocyte- macrophage lineage cells.
(5)_ Specific antibodies to PAF were prepared by immunizing rabbits with a hapten-bovine serum albumin conjugate.
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