| Project/Area Number |
05671805
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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 |
Biological pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NAKAHATA Norimichi TOHOKU UNIVERSITY FACULTY OF PHAMACEUTICAL SCIENCES ASSOCIATE PROFFESSOR, 薬学部, 助教授 (60045804)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | ASTROCYTES / PHOSPHOLIPASE C / PHOSPHOLIPASE D / PHOSPHOLIPASE A_2 / PROSTAGLANDINE_2 / THROMBOXANE A_2 / KAMPO MEDICINE / NEUROTROPHIC FACTOR / ホスホリパーゼC / アストロサイトーマ / グリア細胞 / 分化 / Gタンパク質 / カルシウムイオン / アラキドン酸 |
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| Research Abstract |
In order to clarify the role of astrocytes in brain function, we investigated the signal transduction in astrocytes and obtained the following results.(1) Kampo medicine such as Kakkon-to and san'o-shashin-to potently inhibit prostaglandin E_2 generation in rabbit astrocytes. Ougon (Scutellarie Radix) is a potent inhibitor of phospholipase A_2 in astrocytes. These results suggest that kampo medicines contain substances which inhibit phospholipase A_2. (2) The effect of mastoparan on signal transduction in astrocytes was investigated. Mastoparan inhibits phospholipase C in rabbit astrocytes and 1321N1 human astrocytoma cells. It is demonstrated for the first time that mastoparan activates phospholipase D in a G protein-insensitive manner in 1321N1 human astrocytoma cells. Mastoparan also activates phospholipase A_2 via Gi in rabbit astrocytes. (3) From the analysis of thromboxane A_2 (TXA_2) receptor-mediated signal transduction, TXA_2 receptor is coupled to Gq in human astrocytoma cell
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s and rabbit astrocytes. TXA_2 receptor desensitization in 1321N1 himan astrocytoma cells is divided into two steps, one is uncoupling of TXA_2 receptor and G protein, and the other is its receptor loss from cell surface (downregulation). The mRNA level of TXA_2 receptor is unchanged during TXA_2 receptor desensitization. (4) From the analysis of the effect of bioactive substances marine origin, xestoquinone activates IP_3-induced Ca^<2+> release from store site in 1321N1 human astrocytoma cells. Maitotoxin induces tyrosine kinase-mediated activation of phospholipase C-gamma isoform in a extracellular Ca^<2+>-dependent manner in 1321N1 human astrocytoma cells. 5) Supernatant of glial cell culture potently stimulated the differentiation of PC-12 cells with a potency more than nerve growth factor. The results obtained suggest that astrocytes have several important functions to control central nervous system, and signal transduction of astrocytes may contribute to understand the function of brain. Less
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