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論文
- タイトル
- タイトル（英）
- G protein-coupled receptor 55 activated by palmitoylethanolamide is associated with the development of nocturia associated with circadian rhythm disorders.
- 参照URL
- https://researchmap.jp/read0091842/published_papers/44097630
- 著者
- 著者（英）
- Tatsuya Ihara,Youichi Shinozaki,Eiji Shigetomi,Yosuke Danjo,Sachiko Tsuchiya,Mie Kanda,Manabu Kamiyama,Masayuki Takeda,Schuichi Koizumi,Takahiko Mitsui
- 担当区分
- 概要
- 概要（英）
- AIMS: Bladder function is regulated by clock genes and dysregulation of circadian bladder function can cause nocturia. The blood concentration of palmitoylethanolamide (PEA), a fatty acid metabolite, changes with circadian rhythm. Clock gene abnormalities demonstrate the highest PEA levels during the sleep phase. PEA is a GPR55 agonist that influences urination; therefore, increased PEA during the sleep phase may cause nocturia. Herein, we investigated the function of GPR55 to evaluate the relationship between GPR55 and nocturia that evoked higher PEA during the sleep phase in patients with circadian rhythm disorders. MAIN METHODS: Male C57BL/6 mice were used. GPR55 localization was evaluated by immunofluorescence staining, qRT-PCR, and western blotting. Variations in PEA-induced intracellular Ca2+ concentrations were measured in primary cultured mouse urothelial cells (UCs) using Ca2+ imaging. PEA-induced NGF and PGI2 release in UCs was measured by ELISA. The micturition reflex pathway after PEA administration was evaluated using immunofluorescence staining. KEY FINDINGS: GPR55 was predominant in the UC layer. PEA induced release of Ca2+ from the endoplasmic reticulum into the UC cytoplasm. ELISA and immunofluorescence staining revealed that NGF and PGI2 were released from bladder UCs, stimulated the pontine micturition center in mice, and induced nocturia. SIGNIFICANCE: The loss of regular circadian metabolizing rhythm in fatty acids causes higher blood PEA levels during the sleep phase. Binding of PEA to GPR55 in UC may activate the downstream processes of the micturition reflex, leading to nocturia. These findings suggest a new mechanism for nocturia and its potential as a therapeutic target.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Life sciences
- 巻
- 332
- 号
- 開始ページ
- 122072
- 終了ページ
- 122072
- 出版年月
- 2023年11月1日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.lfs.2023.122072
- 共同研究・競争的資金等の研究課題
研究者
篠﨑 陽一
(シノザキ ヨウイチ)