Can n-3 polyunsaturated fatty acids be new therapeutic agents for overactive bladder?

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K17981
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Toho University
• Principal Investigator: OBARA Keisuke 東邦大学, 薬学部, 講師 (90637422)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ドコサヘキサエン酸（DHA） / エイコサペンタエン酸（EPA） / 膀胱平滑筋 / 消化管平滑筋 / プロスタノイドTP受容体

Outline of Final Research Achievements

This study was carried out to investigate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on urinary bladder smooth muscle (UBSM) and gastrointestinal smooth muscle (GISM) and the intracellular signal transduction via prostanoid TP receptors in UBSM. The results were as follow: 1) Contractile prostanoids stimulate the UBSM TP receptors, and enhanced the UBSM mechanical activities; 2) The UBSM mechanical activities enhanced by TP receptor stimulations were elicited via the activation of Ca2+ channels; 3) The UBSM contractions induced by electrical field stimulation (EFS) was enhanced by a prostanoid TP receptor agonist, and this augmentation was suppressed by DHA; 4) EPA enhances the UBSM mechanical activities; 5) DHA and EPA non-selectively suppressed the GISM contractions.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかとなった収縮性プロスタノイド類のTP受容体を介した膀胱平滑筋の収縮活動を亢進させる性質やTP受容体を介した膀胱収縮活動亢進機構は、膀胱の生理機能の理解や下部泌尿器疾患治療薬の開発に役立つと考えられる。また、EPAが膀胱の収縮活動を亢進する可能性を考慮すると、過活動膀胱患者に対しては魚油の摂取は必ずしも推奨されるものではない可能性が示唆された。さらに、DHA、EPAは消化管平滑筋の収縮を抑制することから、消化管運動が過剰に亢進した状態（例えば炎症性腸疾患）を改善する可能性を有することが示された。