| Project/Area Number |
10356011
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OZAKI Hiroshi Graduate school of Agriculture and Life Sciences, Veterinary Pharmacology, The University of Tokyo, Assoc. Prof., 大学院・農学生命科学研究科, 助教授 (30134505)
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| Co-Investigator(Kenkyū-buntansha) |
FUSETANI Nobuhiro Graduate school of Agriculture and Life Sciences, Marine Biochemistry, The University of Tokyo, Prof., 大学院・農学生命科学研究科, 教授 (70012010)
HORI Masatoshi Graduate school of Agriculture and Life Sciences, Veterinary Pharmacology, The University of Tokyo, Assist. Prof., 大学院・農学生命科学研究科, 助手 (70211547)
KARAKI Hideaki Graduate school of Agriculture and Life Sciences, Veterinary Pharmacology, The University of Tokyo, Prof., 大学院・農学生命科学研究科, 助教授 (60011912)
ISHIDA Yukisato Mitsubishi Kagaku Institute of Life Sciences, Principal Investigator, 生命科学研究所, 主任研究員
MATUNAGA Shigeki Graduate school of Agriculture and Life Sciences, Marine Biochemistry, The University of Tokyo, Assoc. Prof., 大学院・農学生命科学研究科, 助教授 (60183951)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥31,800,000 (Direct Cost: ¥30,600,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2000: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥17,800,000 (Direct Cost: ¥17,800,000)
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| Keywords | actin / denolimerization / biology / pectenotoxin 2 / stellettamides / farnesol / marine sponge / calmodulin / 海洋生物 / 生理活性物質 / 毒素 / カルシウムチャネル / 内皮 / アクチン / ミカロライド / ペクテノトキシン |
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| Research Abstract |
We have isolated and determined several marine metabolites, and analyzed their pharmacological actions to establish the library of novel marine resources. Following are the examples of our pharmacological studies;
1. Pectenotoxin-2: Pectenotixin-2 (PCTX-2), which is one of polyether macrolide toxin isolated from scallops involved in diarrhetic shellfish poisoning, nonselectively inhibited vascular smooth muscle contractions. In A7r5 cell line, PCTX-2 suppressed filamentous actin stress fiber formation detected by FITC-phalloidine staining. PCTX-2 was found to inhibit the velocity and the degree of actin polymerization. Transmission electron microscopic observation disclosed that PCTX-2 specifically damaged apical plasma membranes associated with apical stress fibers via a mat of electron-dense materials in A7r5 cells.
2. Stellettamides: Pharmacological feature of stellettamides, novel sponge derived isoprenoid derivatives containing farnesyl moiety and an alkaloid uni, was investigated. ST-A (30-30μM) inhibited CaM activity. In contrast, ST-C (30-300μM) and farnesol (30-300μM) had little effect on the activity. In the rat aortic smooth muscle cell lines, A7r5 cells, all three compounds significantly inhibited DVC at 10μM. Addition of CaM into the patch pipette reduced the inhibitory action by ST-A in guinea-pig ileal smooth muscle cells. These results indicated that farnesol and ST-C directly inhibits VDC. In contrast, ST-A inhibits VDC through CaM in addition to the direct inhibitory action.
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