| Project/Area Number |
04670377
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | University of Tokyo |
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Principal Investigator |
WATANABE Tsuyoshi Univ.of Tokyo, Dept.of Medicine, Assistant Professor, 医学部(病), 助教授 (80158641)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAMOTO Kazuhisa Univ.of Tokyo, Dept.of Medicine, Assistant Professor, 医学部(病), 助手 (20251233)
HIGASHIHARA Masaaki Univ.of Tokyo, Dept.of Medicine, Assistant Professor, 医学部(病), 助手 (80165084)
NAKAO Akihide Univ.of Tokyo, Dept.of Medicine, Assistant Professor, 医学部(病), 助手 (10159056)
HASHIMOTO Yoshiaki Univ.of Tokyo, Dept.of Medicine, Assistant Professor, 医学部(病), 助手 (40172879)
SHIMIZU Takao Univ.of Tokyo, Dept.of Bichemistry, Professor, 医学部, 教授 (80127092)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Prostaglandin / Thoromboxane / Platelet-activating factor / Receptor / GTP-binding protein / Megakaryocytes / Vascular smooth muscle cells / Fibroblasts / 巨核芽細胞 / 糸球体メサンギウム細胞 / 血管平滑筋 |
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| Research Abstract |
1)Mechanisms of regulation of expression of lipid mediator receptors in megakaryocytic cell line ; MEG-01, vascular smooth muscle cells, fibroblasts and glomerular mesangial cells--- We found that expression of thromboxane (TX)A_2 andprostaglandin (PG)I_2 receptors were regulated by the action of protein kinase C and homologously desensitized by their own agonist in MEG-01 cells. It was also found that platelet-activating factor (PAF) receptor expression was regulated by lipopolysacharide (LPS) and cAMP in glomerular mesangial cells. Technically, we developed a new RT-PCR system for quantitation of mRNA in minute samples (ref.5 and 11).
2)Sinal transduction mechanisms--- We characterized the PGF_2 alpha receptor andidentified its coupled GTP-binding protein as Gq (ref.6). We also disclosed PGF_2 alpha receptor-mediated tyrosine phosphrylation of celular components in intracellular Ca^<2+>-dependent manner and that this tyrosine phosphorylation may play a physiological role in mitogenesis in NIH-3T3 cells. Recently, we further found PGF_2 alpha receptor-mediated activation of mitogen-activated protein (MAP) kinases.
3)Mechanisms of Cross-talk--- We analyzed the mechanisms of cross-talks between signalling pathways of PGI_2 and TXA_2 receptors in MEG-01 cells. We are now trying to develop specific antibodies against lipid mediator receptors using molecular biological techniques for further analysis of molecular mechanisms of these phenomena.
4)Effects of receptor antagonists for lipid mediator--- Trial of PAF receptor antagonist (WEB2086) and TXA_2 synthetase inhibitor (OKY046) are now being tested on a hyperchlesterolemic rabbit model for atherosclerosis.
5)Cloning--- We have cloned various subtypes of GTP-binding proteins from aguinea piglung cDNA library (ref.1).
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