| Project/Area Number |
07101002
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Cardiovascular Center Research Institute (1997-1998)
Kyoto University (1995-1996) |
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Principal Investigator |
MASAKI Tomoh National Cardiovascular Center Research Institute, Director General, 所長 (60009991)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAMURA Tatsuya National Cardiovascular Center Research Institute, Head, バイオサイエンス部, 室長 (30243033)
岡本 安雄 京都大学, 医学研究科, 助手
二宮 治明 京都大学, 医学研究科, 助手 (80212124)
三輪 聡一 京都大学, 医学研究科, 助教授 (40157706)
比企 一晃 京都大学, 医学研究科, 助手 (30263099)
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| Project Period (FY) |
1995 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥283,000,000 (Direct Cost: ¥283,000,000)
Fiscal Year 1998: ¥23,000,000 (Direct Cost: ¥23,000,000)
Fiscal Year 1997: ¥63,000,000 (Direct Cost: ¥63,000,000)
Fiscal Year 1996: ¥82,000,000 (Direct Cost: ¥82,000,000)
Fiscal Year 1995: ¥115,000,000 (Direct Cost: ¥115,000,000)
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| Keywords | vascular endothelium / endothelin / nitric oxide / oxidized LDL / endothelin receptor / vasoconstriction / cell growth, dystroglycan / ジストログリカン / 変性LDL受容体 / アルギニン輸送体 / 非選択的カチオンチャネル / 受容体輸送活性相関 / 変成LDL受容体 / 電位依存性カルシウムチャネル / 非選択的陽イオンチャネル / エンドセリン変換酵素 / カチオンチャネル |
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| Research Abstract |
To elucidate regulatory role for endothelium in local vascular function. we have studied cellular and subcellular mechanisms of endothelin(ET) action and interaction between ET and nitric oxide(NO). A novel endothelial receptor for oxidized LDL was cloned. It phagocytized the aged blood cells and the apoptized cells as well as oxidized LDL.It also suppressed NO synthesis via inhibition of cationic amino acid transporter, and increased ET synthesis. ET induced smooth muscle contraction by activation of non-selective cation channel sensitive to SK&F96365. This channel was also inhibited by NO.Both ET_A and ET_B coupled to Galphas, Galphai, and Galphaq. However, each of these Galpha proteins bound to different part of the domain of ET receptor. Palmitoylation of C-terminal cystein residues of ET receptor was particularly important to the binding of Galphai and Galphaq. Cell growth activity of ET was mediated by three ways, i.e. activation of protein kinase C, phosphoinositide 3-kinase, and thyrosin kinase pathways. MAP kinase was activated in every pathway. Dystroglycan was shown to be expressed in endothelium. It was shown that dystroglycan regulated motility of endothelial cells.
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