2004 Fiscal Year Final Research Report Summary
A study for role of PGE2 on adhesion of mast cells to fibronectin
| Project/Area Number |
15390024
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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 | Mukogawa Women's University |
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Principal Investigator |
ICHIKAWA Atsushi Mukogawa Women's University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (10025695)
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| Co-Investigator(Kenkyū-buntansha) |
SENMA Masanori Mukogawa Women's University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90098533)
SUGIMOTO Yukihiko Kyoto University, Associate Professor, 薬学研究科, 助教授 (80243038)
TANAKA Satoshi Kyoto University, Lecturer, 薬学研究科, 助手 (40303846)
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| Project Period (FY) |
2003 – 2004
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| Keywords | mast cells / cell adhesion / prostaglandin E2 / Extracellular matrix / cAMP / Epac / Ca2+ |
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| Research Abstract |
The purpose of this project is to determine the mechanism of mast cell adhesion to fibronectin. Mastocytoma P-815 cells were cultured on a plate pre-coated with or without fibronectin in 5%-FCS containing Fisher medium, and incubated with PGE2 for various times at 37℃ in 5% C02-incubator. Obtained results are shown below ;
1.P-815 cells were adhered to fibronectin in response to 10^<-8> M-10^<-6> M PGE2. The adherence activity of PGE2 was appeared through its binding to EP4 receptors expressed on P-815 cells, followed by a stimulated cAMP formation and cAMP-dependent protein kinase A activity. These responses were not demonstrated up to 4-5 hrs after PGE2 addition, indicating involvement of newly formed unknown proteins, which have been searching thereafter.
2.After initiation of PGE2-induced P-815 cell adhesion to fibronectin, being inhibited by PKA inhibitor H-89, adhered P-815 cells did not leak out by H89 treatment. However, PGE2-adhered P-815 cells were easily detached by a decrease of increasing intracellular Ca2+ level by treatment with EGTA,BAPTA/AM, and SKF96365, a Ca2+ channel ROCC inhibitor. Really, adhered P-815 cells were found to consist of high intracellular Ca2+ level.
3.PGE2-activated P-815 cell adhesion to fibronectin were mostly suppressed by incubation with CaM kinase inhibitor.
4.CAMP/PKA-independent signals were extensively searched for, and as a result have determined involvement of Epac signal (exchange protein directly activated by cAMP) as important candidatet molecules.
From these results, we have presented that PGE2-activated P-815 cell adhesion might be comprised of two signals, first during binding initiation phase cAMP/PKA dependent reactions involved in while during late binding maintenance phase Epac reactions did. These results are surely important to resolve mast cell adhesion ability to extra-cellular matrix like ibronectin in local inflammatory tissues.
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[Journal Article] A cluster of aromatic amino acids in the i2 loop plays a key role for Gs coupling in prostaglandin EP2 and EP3 receptors2004
Author(s)
Sugimoto, S., Nakato, T., Kita, A., Tabara, H., Tanaka, S., Ichikawa, A.
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Journal Title
J.Biol.Chem. 279
Pages: 11016-11026
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Expression of L-histidine decarboxykase in granules of elicited mouse mastocytoma P-815 cells2004
Author(s)
Tanaka, S., Deai, K., Takahashi, K., Yamane, H., Sugimoto, Y., Ichikawa, A.
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Journal Title
Eur.J.Immunol 34
Pages: 1472-1482
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A cluster of aromatic amino acids in the i2 loop plays a key role for Gs coupling in prostaglandin EP2 and EP3 receptors.2004
Author(s)
Sugimoto, Y., Nakato, T., Kita, A., Takahashi, Y., Hatae, N., Tabata, H., Tanaka, S., Ichikawa, A.
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Journal Title
J.Biol.Chem. 279
Pages: 11016-11026
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional domains essential for Gs activity in prostaglandin EP2 and EP3 receptors.2004
Author(s)
Sugimoto, Y., Nakato, T., Kita, A., Hatae, N., Tabata, H., Tanaka, S., Ichikawa, A.
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Journal Title
Life Sci. 74
Pages: 135-141
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP42003
Author(s)
Hatae, N., Kita, A., Sugimoto, Y., Tanaka, S., Ichikawa, A.
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Journal Title
J.Biol.Chem. 278
Pages: 17977-17981
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors2003
Author(s)
Oka, T., Oka, K., Kobayashi, T., Ichikawa, A., Ushikubi, F., Narumiya, S.
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Journal Title
J.Physiol. 551
Pages: 945-954
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Induction of adherent activity in nastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4.2003
Author(s)
Hatae, N., Kita, A., Tanaka, A., Sugimoto, Y., Ichikawa, A.
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Journal Title
J.Biol.Chem. 278
Pages: 17977-17981
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors.2003
Author(s)
Oka, T., Oka, K., Kobayashi, T., Sugimoto, Y., Ichikawa, A., Ushikubi, F., Narumiya, S., Saper, C.B.
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Journal Title
J.Physiol. 551
Pages: 945-954
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification and characterization of a novel progesterone receptor-binding element in the mouse prostaglandin E receptor subtype EP2 gene.2003
Author(s)
Tsuchiya, S., Tanaka, S., Sugimoto, Y., Katsuyama, M., Ikegami, R., Ichikawa, A.
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Journal Title
Genes to Cells 8
Pages: 747-758
Description
「研究成果報告書概要(欧文)」より
