Functions of bladder muscularis mucosae during storage phase as a new therapeutic target

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: Hashitani Hikaru 名古屋市立大学, 医薬学総合研究院(医学), 教授 (10315905)
• Co-Investigator(Kenkyū-buntansha): 西川 信之 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (30722748) ; 三井 烈 名古屋市立大学, 医薬学総合研究院(医学), 講師 (90434092)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 粘膜筋板 / 排尿筋 / 過活動膀胱 / アンジオテンシン / NO神経 / 自発収縮

Outline of Final Research Achievements

Contractile properties of muscularis mucosae (MM), the predominant contractile element in the bladder mucosa, was compared with those of detrusor smooth muscle (DSM). MM develops vigorous spontaneous phasic contractions arising from bursting action potential firing but modestly responds to the excitatory, cholinergic innervation, suggesting that it play its major role during storage rather than voiding phase. Unlike DSM lacking inhibitory innervation, MM receives the inhibitory nitrergic innervation. MM also exhibits a much greater sensitivity to angiotensin II (ATII) than DSM that could well sense circulating concentration of ATII, suggesting that MM is the predominant target of contractile actions of ATII in the bladder. The MM contractility appears to be diminished by as yet unidentified substance released from the urothelium. The contractile properties of MM could be a novel therapeutic target in the treatment of overactive bladder.

Free Research Field

平滑筋生理学

Academic Significance and Societal Importance of the Research Achievements

過活動膀胱は、加齢やメタボリック症候群にともない発症が増加するが、その病態は十分に解明されていない。膀胱には排尿時の収縮を担う排尿筋に加えて粘膜筋板が存在するが、その役割は排尿時ではなく蓄尿時において重要であると考えられる。粘膜筋板は、血中濃度でも収縮応答する高いアンジオテンシン(ATII)感受性を有し、ATIIが増加する病態での過活動膀胱発症に関わっている可能性がある。粘膜筋板の収縮特性には排尿筋との違いが認められ、排尿時の膀胱収縮を抑制しない新たな治療標的となる可能性が示された。