| Project/Area Number |
02404079
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ICHIKAWA Atsushi Kyoto University,Physiological Chemistry Professor, 薬学部, 教授 (10025695)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Tetsuya Kyoto University,Physiological Chemistry Associate Professor, 薬学部, 助教授 (90111971)
YATSUNAMI Kimio Kyoto University,Physiological Chemistry Instructor (30191141)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥23,300,000 (Direct Cost: ¥23,300,000)
Fiscal Year 1992: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1991: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1990: ¥13,500,000 (Direct Cost: ¥13,500,000)
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| Keywords | mast cell / inflammatory cells / histamine synthesis / endothelial cells / prostaglandins / PGE_2 subtype / PGE_2 receptor / PGI_2 receptor / プロスタグランジン / プロスタサイクリン / プロスタグランジンE_2 / MARCS蛋白 / ヘムオシゲナーゼ / △^<12>-PGJ_2 / ヒスタミン / ヒスチジン脱炭酸酵素 / トロンビン / プロテインキナ-ゼC / サイクリックAMP / 血管内皮細胞 / 炎症 / プロスタグランジンD_2 / プロスタグランジンレセプタ- / FGF |
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| Research Abstract |
We have investigated the basic problems about the action mechanisms of bioactive molecules which control the reciprocal relation between mast cells and other inflammatory cells, focused on following three points. 1. Studies on histamine synthesis in mast cells. (1) Isolation of L-histidine decarboxylase from mouse mastocytoma P-815 cells was performed, and is cDNA-derived amino acid sequence was determined. (2) Synergistic effects of de novo synthesis of L-histidine decarboxylase and its mRNA was found in cultured mast cells treated with two different stimulants; dexamethasone and 12-O-tetradecanoylphorbol 13-acetate, or dibutyryl cAMP and calcium ionophore A23187. (3) Possible post-translational processing of L-histidine decarboxylase was suspected. 2. Studies on cellular interaction between mast cells and endothelial cells or platelets. (1) PGD_2, is metabolite DELTA^<12>-PGJ_2, from mast cells inhibited cell growth of, but induced 31kDa protein, which was hemeoxygenase, in endothelial cells. (2) PGI_2 from endothelial cells stimulated cAMP synthesis via Gs-coupled adenylate cyclase. (3) Differential regulation of thrombin- or ATP-induced mobilization of intracellular Ca_<2+> by PGI_2 receptor in mastocytoma cells. (4) PGI_2 receptors in mastocytoma cells and platelets were identified by use of irreversible specific photoaffinity probe. 3. Studies on structure and function of prostaglandin E receptor subtypes. and on their mRNA expression in various tissues. (1) Cloning and expression of cDNAs for mouse prostaglandin E receptors, EP_3 subtype and EP_2 subtypes. (2) Functional cDNA for two isoforms of PGE receptor EP_3 subtype with different C-terminal domains which were derived from alternative splicing were obtained. Two forms determined ligand-binding affinity and sensitivity of agonist-induced desensitization.
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