Development of novel antihypertensive drugs and diuretics with exocytosis assay using chemical library

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893064
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nomura Naohiro 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (50735800)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: アクアポリン２ / EGFR

Outline of Final Research Achievements

Aquaporin 2 (AQP2) is expressed on apical membrane in renal collecting ducts, and it plays an important role in regulation of urine concentration. The mutation of AQP2 causes nephrogenic diabetes insipidus. In the previous study of exocytosis screening assay of AQP2, epidermal growth factor receptor (EGFR) was identified to be involved in the regulation of AQP2 trafficking. In this study, we used Erlotinib, a EGFR inhibitor, and showed that Erlotinib increased in the apical membrane accumulation of AQP2, which improved the urine volume and osmolarity of the NDI model rats. We also showed the phosphorylation of AQP2 was involved in the mechanism of the EGFR inhibitor, which was independent of cAMP and PKA activity.

Free Research Field

腎臓内科