| Project/Area Number |
62480421
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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 Univ. Dept. of Pharmacology: Prof., 薬学部, 教授 (10025695)
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| Co-Investigator(Kenkyū-buntansha) |
YATSUNAMI Kimio Kyoto Univ. Dept. of Pharmacology: Assist., 薬学部, 助手 (30191141)
SAITO Terumi Kyoto Univ. Dept. of Pharmacology: Ass. Prof., 薬学部(昭和62,63年度), 助教授 (80025717)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Inflammation / Mast cell / Endothelial cell / Histamine / PGD_2 / Histidine decarboxylase / Calcium / Glucocorticoid / 炎症 / プロスタグランジンD_2 / サイクリックAMP / ヒスタミン生合成酵素 / 血小板 |
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| Research Abstract |
This research project was intended to investigate the multifunction of mast cells in conjunction with or without other cells in inflammation tissues.
1 Control of mast cell function in release and synthesis of histamine. (1) Histamine releasing activity; active tridecamer of compound 48/80, a Ca^<2+>-dependent histamine releaser, was synthesized. The binding of tridecamer induced a rapid accumulation of the arachidonic acid into PA, PI and PC, with concomitant decrease of arachidonic acid from PE prior to the detectable histamine release. (2) Histamine synthesizing activity; histidine decarboxylase in mast cells has first been purified to electrophoretic homogeneity, which has two identical subunits having Mr=31 kDa on SDS-PAGE. The de novo synthesis of the enzyme in mastocytoma cells was stimulated by glucocorticoid in conjunction with activated protein kinase C. (3) Prostaglandin (PG) activity; PGD_2 binding to mast cell membrane is possibly controlled through phosphorylation-dephosphorylation of the receptor itself.
2. Interaction of mast cell to other cells. (1) Mast cells to endothelial cells; PGD_2/ PGJ_2 from mast cells induced a de novo synthesis of a new 31 kDa protein in endothelial celts. (2) PGD_2 from mast cells enhanced reaction of neutrophil adhesion to endothelial cells, which activity is more potent than that of LTB_4. (3) Predifferentiated mast cells are capable of adhering to activated endothelial cells by TPA treatment, which stimulates unidentified protein synthesis by the action of protein kinase C.
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