2001 Fiscal Year Final Research Report Summary
Pharmacological study of intarcellular signal transduction using marine natural products as pharmacological tools.
| Project/Area Number |
12470492
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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 | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
OHIZUMI Yasushi Grad. School Pharm. Sci., Tohoku University, Professor, 大学院・薬学研究科, 教授 (00006355)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Shin-ya Grad. School Pharm. Sci., Tohoku University, Res. Instructor, 大学院・薬学研究科, 助手 (80271849)
MATSUNAGA Kimihiro Grad. School Pharm. Sci., Tohoku University, Res. Instructor, 大学院・薬学研究科, 講師 (90222306)
NAKAHATA Norimichi Grad. School Pharm. Sci., Tohoku University, Professor, 大学院・薬学研究科, 教授 (60045804)
NAKATANI Keigo Grad. School Pharm. Sci., Tohoku University, Res. Associate, 大学院・薬学研究科, 教務職員 (60281979)
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| Project Period (FY) |
2000 – 2001
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| Keywords | marine natural product / Ca^<2+> channel / Ca^<2+> release / PI-3 kinase / actin / smooth muscle |
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| Research Abstract |
The study of intracellular signal transduction achieved a great advance in these days. However, highly selective pharmacological tools are still required for usage. In our study, we have search the bioactive compounds which target to intracellular signal transduction pathway, isolated from marine organisms and have applied as pharmacological tools. Here, we have succeeded in finding the compounds which affect from input to output of intracellular signal transduction pathway such as on (1) intracellular Ca mobilization, (2) PI-3 kinase, and (3) cytoskelton. Gramine analogues isolated from barnacle showed potent vasorelaxing activity on aortic smooth muscle. This effect was mediated by inhibition of voltage dependent Ca channel. Bisplacin isolated from marine sponge promoted Ca release from sarcoplasmic reticulum with same mechanism as caffeine. We have studied structure-activity relationship of eudistomin D, the known Ca releaser. Halogens in C-5 and C-7 of β-carboline are shown to be necessary for Ca release. Furthermore, methyl moiety in C-9 also representing critical role in Ca releasing activity.
We have also studied the role of PI-3 kinase in apoptosis by using halenaquinone isolated from marine sponge as pharmacological tool. We have also showed that goniodomin A which affect on cytoskelton inhibit cell migration.
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Research Products
(12 results)
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[Publications] Suzuki, A., Matsunaga, K., Shin, H., Tabudrav, J, Shizuri, Y. & Ohizumi, Y.: "Bisprasin, a novel Ca^<2+> releaser with caffeine-like properties from a marine sponge, Dysidea spp., acts on Ca^<2+>-induced Ca^<2+> release channels of skeletal muscle sarcoplasmic reticulum"J. Pharmacol. Exp. Ther.. 292. 725-730 (2000)
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[Publications] Fujiwara, H., Matsunaga, K., Saito, M., Hagiya, S., Furukawa, K., Nakamura, H. & Ohizumi, Y.: "Halenaquinone, a novel phosphatidylinositol 3-kinase inhibitor from a marine sponge, induces apoptosis in PC12 cells."Eur. J. Pharmacol.. 413. 37-45 (2001)
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[Publications] Ohi, Y., Atsuki, K., Torii, Y., Ohizumi, Y., Watanabe, M. & Imaizumi, Y.: "Imaging of Ca^<2+> release by caffeine and 9-methyl-7-bromoeudistomin D and the associated activation of large conductance Ca^<2+>-dependent K^+ channels in urinary bladder smooth muscle cells of the guinea pig."Jpn. J. Phramacol.. 85. 382-390 (2001)
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[Publications] Abe, M., Inoue, D., Matsunaga, K. Ohizumi, Y. Ueda, H., Asano, T., Murakami, M. & Sato, Y.: "Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells."J. Cell. Physiol.. 190. 109-116 (2002)
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