Basic and clinical studies of the adrenomedullin receptor

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: University of Miyazaki
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• 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

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.

Free Research Field

循環器内科学