Basic and clinical studies of the adrenomedullin receptor
| Project/Area Number |
15K09124
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | University of Miyazaki |
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Principal Investigator |
Kuwasako Kenji 宮崎大学, フロンティア科学実験総合センター, 准教授 (20381098)
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| Co-Investigator(Kenkyū-buntansha) |
北村 和雄 宮崎大学, 医学部, 教授 (50204912)
永田 さやか 宮崎大学, 医学部, 助教 (00452920)
加藤 丈司 宮崎大学, フロンティア科学実験総合センター, 教授 (20274780)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ペプチド / G蛋白共役型受容体 / 心血管病 / 分子調節機構 / 臨床応用 |
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| Outline of Final Research Achievements |
Adrenomedullin (AM) is a potent hypotensive peptide and can mediate multi-protective signaling through type 1 AM receptors (AM1 receptors), which consist of calcitonin receptor-like receptor (CLR), a G protein-coupled receptor (GPCR), and GPCR activity-modifying protein 2 (RAMP2). Here we elucidated the molecular basis and mechanism of GPCR kinases (GRKs) and beta-arrestins, both of which interact with the cytoplasmic C-terminal tail of the human (h)AM1 receptors. We also clarified the molecular mechanism by which protein kinase C (PKC) induces the internalization of the hAM1 receptors in the absence of AM. Furthermore, we elucidated the mechanism of the intracellular trafficking and signaling of the hAM1 receptors using their stable transfectants and found an effective strategy that can promote their re-sensitization.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Calcitonin-typical suppression of osteoclastic activity by amphioxus calcitonin superfamily peptides and insights into the evolutionary conservation and diversity of their structures.2017
Author(s)
Sekiguchi, T., Shiraishi, A., Satake, H., Kuwasako, K., Takahashi, H., Sato, M., Urata, M., Wada, S., Endo, M., Ikari, T., Hattori, A., Srivastav, A.K. and Suzuki, N.
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Journal Title
Gen. Comp. Endocrinol.
Volume: 246
Pages: 294-300
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor.2016
Author(s)
Kuwasako, K., Sekiguchi, T., Nagata, S., Jiang, D., Hayashi, H., Murakami, M., Hattori, Y., Kitamura, K. and Kato, J.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 470
Issue: 4
Pages: 894-899
DOI
Related Report
Peer Reviewed
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[Journal Article] Evidence for conservation of the calcitonin superfamily and activity-regulating mechanisms in the basal chordate Branchiostoma floridae: insight into the molecular and functional evolution in chordates.2016
Author(s)
Sekiguchi, T., Kuwasako, K., Ogasawara, M., Takahashi, H., Matsubara, S., Osugi, T., Muramatsu, I., Sasayama, Y., Suzuki, N., and Satake, H.
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Journal Title
J. Biol. Chem.
Volume: 291
Issue: 5
Pages: 2345-2356
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.2015
Author(s)
Murakami M, Yoshikawa T, Nakamura T, Ohba T, Matsuzaki Y, Sawamura D, Kuwasako K, Yanagisawa T, Ono K, Nakaji S, Yanai K.
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Journal Title
Biochem Biophys Res Commun.
Volume: 458
Issue: 3
Pages: 584-589
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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