| Project/Area Number |
08457603
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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 Tohoku University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (00006355)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Keigo Tohoku University, Faculty of Pharmaceutical Sciences Research Associate, 薬学部, 教務職員 (60281979)
FURUKAWA Ken-Ichi Tohoku University, Faculty of Pharmaceutical Sciences Assistant Professor, 薬学部, 助手 (20165468)
NAKAHATA Norimichi Tohoku University, Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (60045804)
松永 公浩 東北大学, 薬学部, 助手 (90222306)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | marine products / plateles / muscle cells / Ca^<2+> / platelete aggregation / ATPase / thromboxane A_2 / 9-methyl-7-bromoeudistomin D / Ca^<2+>遊離チャネル / BKチャネル / 形態変化 / 蛋白リン酸化 / IIb-IIIa / 筋収縮 |
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| Research Abstract |
In our screening program for natural products from marine organisms, useful not only for basic researches but also for the treatment of a variety of diseases, we have studies the mechanism of action of these compounds. The new monogalactopyranosylacylglyceroI was isolated from the cultured marine alga and caused an inhibition of platelet aggregation. Theonezolide-A (TZ-A), a novel polyketide macrolide caused a marked platelet shape change. Our pharmacological studies on this compound suggest that TZ-A is a useful chemical tool for clarifying the signal transduction mechanism. Zooxanthellatoxin-A (ZT-A) from a symbiotic dinoflagellate caused Ca^<2+>-or thromboxane A_2-dependent and genestin-sensitive aggregation of platelets. It is suggested that ZT-A primarily activate a protein tyrosine kinase and that the activated protein tyrosine kinase subsequently stimulates the activation of mitogen-activated protein kinase probably via PLC-gamma2 and PKC.On the other hand, ptilomycalin A has been showm to interacts competitively with ATP at the ATP binding site of Na^+, K^+-ATPase or Ca^<2+>-ATPaase, resulting in inhibition of both the enzymes. Recently, we have found that 9-methyl-7-bromo-eudistomin D,the most powerful caffeine like substances not but caffeine failed to induce a contraction of skinned smooth muscles. These data suggest that intracellular Ca^<2+> stores consist of two functional distinct types. These studies lead to the conclusion that these natural products are useful not only as pharmacological tools but also as leading compounds for new drug development.
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