1999 Fiscal Year Final Research Report Summary
FUNCTIONAL REGULATION OF RECEPTORS FOR LIPID MEDIATORS
| Project/Area Number |
10558101
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Functional biochemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IZUMI Takashi University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70232361)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHIKO Shigeru Meiji Seika Kaisha, LTD, Pharmaceutical Research Center, Drug Discovery, Director, 創薬研究所探索薬理室, 室長(研究職)
KUME Kazuhiko University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助手 (30251218)
SHIMIZU Takao University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80127092)
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| Project Period (FY) |
1998 – 1999
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| Keywords | LIPID MEDIATORS / PAF / LEUKOTRIENES / RECEPTORS / TRANSCRIPTIONAL REGULATION |
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| Research Abstract |
Lipid mediators such as leukotrienes (LTs) and platelet-activating factor (PAF) are major chemical mediators involved in inflammatory and allergic disorders. Despite their potent biological activities, little is known about the function and translational regulation of their receptors. To clarify these questions, we carried out following experiments and obtained some results that may contribute better understanding of patho-physiological roles of lipid mediators and development of new therapies and drugs for inflammatory and at11ergic disorders.
1. We analyzed the mechanisms of ligand-induced internalization of PAP receptors.
2. Using PAP receptor knockout mice and cPLA2 knockout mice, the roles of lipid mediators in acute lung injuries occurred by LPS and acid were investigated.
3. Functional coupling of LTB4 receptor with G-proteins in porcine WBC was identified.
4. Analysis of human genome for LTB4 receptor was carried out. The mechanisms for leukocyte specific expression of LTB4 receptor was clarified.
5. cDNA clones for LTB4 receptors of mouse, rat and Guinea pig were identified. And their functions were analyzed.
6. We analyzed the signal transduction mechanisms through LTD4 receptors using human monocytic leukemia THP-1 cells.
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[Publications] Noiri, E., Yokomizo, T., Nakao, A., Izumi, T., Fujita, T., Kimura, S., Shimizu, T.: "An in vivo approach showing the chemotactic activity of leukotriene B4 in acute renal ischemic-reperfusion injury"Proc Natl Acad Sci USA. 97. 823-828 (2000)
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「研究成果報告書概要(和文)」より
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[Publications] Nagase, T., Ishii, S., Kume, K., Uozumi, N., Izumi, T., Ouchi, Y., Shimizu, T.: "Platelet-activating factor mediates acid-induced lung injury in genetically engineered mice"J Clin Invest. 104. 1071-1076 (1999)
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[Publications] Toda, A., Yokomizo, T., Masuda, K., Nakao, A., Izumi, T., Shimizu, T., Fujita, T., Kimura, S., Shimizu, T.: "Cloning and characterization of rat leukotriene B4 receptor"Biochem Biophys Res Commun. 262. 806-812 (1999)
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[Publications] Fukusawa, K.M., Fukusawa, K., Harada, M., Hirose, J., Izumi, T., Shimizu, T.: "Aminopeptidase B is structurally related to leukotriene-A4 hydrolase but is not a bifunctional enzyme with epoxide hydrolase activity"Biochem J. 339. 492-502 (1999)
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[Publications] Igarashi, T., Yokomizo, T., Tsutsumi, O., Taketani, Y., Shimizu, T., Izumi, T.: "Characterization of the leukotriene B4 receptor in porcine leukocytes. Separation and reconstitution with heterotrimeric GTP-binding proteins"Eur J Biochem.
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[Publications] Ishii, I., Saito, E., Izumi, T., Ui, M., Shimizu, T.: "Agonist-induced sequestration, recycling, and resensitization of platelet-activating factor receptor. Role of cytoplasmic tail phosphorylation in each process"J Biol Chem. 273. 9878-9885 (1998)
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