MP54-19 THE DISRUPTED CIRCADIAN RHYTHM OF THE FATTY ACID METABOLITE, PALMITOYLETHANOLAMIDE, INDUCES NOCTURIA THROUGH G PROTEIN-COUPLED RECEPTOR 55 ACTIVATION IN THE BLADDER

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP54)1 Apr 2020MP54-19 THE DISRUPTED CIRCADIAN RHYTHM OF THE FATTY ACID METABOLITE, PALMITOYLETHANOLAMIDE, INDUCES NOCTURIA THROUGH G PROTEIN-COUPLED RECEPTOR 55 ACTIVATION IN THE BLADDER Tatsuya Ihara*, Takahiko Mitsui, Sachiko Tsuchiya, Mie Kanda, Satoru Kira, Hiroshi Nakagomi, Manabu Kamiyama, Yoichi Shinozaki, Norifumi Sawada, Shuichi Koizumi, and Masayuki Takeda Tatsuya Ihara*Tatsuya Ihara* More articles by this author , Takahiko MitsuiTakahiko Mitsui More articles by this author , Sachiko TsuchiyaSachiko Tsuchiya More articles by this author , Mie KandaMie Kanda More articles by this author , Satoru KiraSatoru Kira More articles by this author , Hiroshi NakagomiHiroshi Nakagomi More articles by this author , Manabu KamiyamaManabu Kamiyama More articles by this author , Yoichi ShinozakiYoichi Shinozaki More articles by this author , Norifumi SawadaNorifumi Sawada More articles by this author , Shuichi KoizumiShuichi Koizumi More articles by this author , and Masayuki TakedaMasayuki Takeda More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000916.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It is reported that the bladder functions are under the regulation of clock genes, which regulate circadian rhythm in organisms, and dysregulation of circadian bladder function can cause nocturia. In humans, some of the fatty acid metabolite levels are higher in nocturia patient plasma compared to non-nocturia patient. Especially, Palmitoylethanolamide (PEA) showed highest level, which are known as an agonist of G protein-coupled receptor 55 (GPR55). In the present study, we investigated the dynamics and effect of PEA on GPR55 in the mice bladder to evaluate the relationship between nocturia and lipid metabolism. METHODS: Male C57BL/6 (WT) mouse and Clock mutant mouse (ClockΔ19/Δ19) were used. ClockΔ19/Δ19 mouse deficit a function of Clock, which is one of clock genes, and showed nocturia phenotype. They were bred 12 h dark/light condition. PEA concentration in the mouse serum was measured using LS/MS every 8 hour for 2 days and compared between WT and ClockΔ19/Δ19 mice. PEA (10 mg/kg) was administered intraperitoneally (ip) in WT mice under the constant dark condition, and urination pattern was recorded for 2 days using metabolic cages. GPR55 distribution in mice was evaluated using Immunofluorescence staining, RT-PCR, and Western blotting. The PEA induced intracellular Ca2+ variations was measured in the mouse primary cultured urothelial cells (UCs) using Fura2-AM Ca2+ imaging. RESULTS: Serum PEA concentration fluctuated with circadian rhythm in WT mice, which was lower during light phase. However, those in ClockΔ19/Δ19 mice were in constant and higher-level during sleep phase. The voiding frequency was increased, and bladder capacity was decreased after PEA ip in WT mice. GPR55 was predominant at bladder urothelial cell layer. The intracellular Ca2+ was increased after PEA stimulation, also under extracellular Ca2+ free condition in UCs. These changes were inhibited by an endoplasmic reticulum (ER) inhibitor (Fig. 1). CONCLUSIONS: These results indicated that clock gene abnormalities cause higher serum PEA level in mice. PEA can activate GPR55 in the bladder urothelium, then mobilizes Ca2+ in the ER to cytoplasm and triggers the micturition reflex. The development of new drugs for GPR55 may leads to nocturia treatment. Source of Funding: no competing financial interests. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e799-e799 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tatsuya Ihara* More articles by this author Takahiko Mitsui More articles by this author Sachiko Tsuchiya More articles by this author Mie Kanda More articles by this author Satoru Kira More articles by this author Hiroshi Nakagomi More articles by this author Manabu Kamiyama More articles by this author Yoichi Shinozaki More articles by this author Norifumi Sawada More articles by this author Shuichi Koizumi More articles by this author Masayuki Takeda More articles by this author Expand All Advertisement PDF downloadLoading ...