The functional analysis of the calcium sensing receptor in the inner ear, and exploration of its application

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Nagoya City University
• Principal Investigator: Inagaki Akira 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (70405166)
• Co-Investigator(Kenkyū-buntansha): 鵜川 眞也 名古屋市立大学, 医薬学総合研究院(医学), 教授 (20326135) ; 山村 寿男 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (80398362) ; 関谷 真二 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (50770591)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: カルシウム感知受容体 / 内耳 / 聴覚

Outline of Final Research Achievements

We attempted to clarify its function in the calcium homeostasis in the cochlea by developing knockout mice, those lack calcium sensing receptor to identify its function in the inner ear. However, the elimination of calcium sensing receptor brought lethality in the offspring, therefore we tried to develop double knockout mice to ameliorate its effects in the off-target organs. Unfortunately, the attempt has not succeeded. Therefore, we focused on the pharmacological suppression of the calcium sensing receptor. In the previous project, we injected antagonists to the perilymphatic space in the inner ear directly, which hamper a various analysis due to its surgical invasiveness. To overcome this, we focused on the drug transfer in the targeted tissues, and identified the level of the drug transfer level by using tandem mass spectrometry. These outcomes are anticipated to be a reference for the further analysis in the field in the near future.

Free Research Field

聴覚

Academic Significance and Societal Importance of the Research Achievements

聴力は社会への参加に必要なコミュニケーションになくてはならない、必要不可欠な機能である。本研究の成果は、将来的にカルシウムの恒常性異常による聴覚異常に対する介入店となる可能性がある。カルシウムの恒常性異常による聴覚異常の一つに加齢性難聴が挙げられ、今後高齢化社会を迎えるにあたり、本研究の成果がそれらに対する対応策を講ずるための一助となりえる。