Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase

• Published in: Scientific reports Vol. 6; no. 1; p. 29761
• Main Authors: Nakagomi, Hiroshi, Yoshiyama, Mitsuharu, Mochizuki, Tsutomu, Miyamoto, Tatsuya, Komatsu, Ryohei, Imura, Yoshio, Morizawa, Yosuke, Hiasa, Miki, Miyaji, Takaaki, Kira, Satoru, Araki, Isao, Fujishita, Kayoko, Shibata, Keisuke, Shigetomi, Eiji, Shinozaki, Youichi, Ichikawa, Reiko, Uneyama, Hisayuki, Iwatsuki, Ken, Nomura, Masatoshi, de Groat, William C., Moriyama, Yoshinori, Takeda, Masayuki, Koizumi, Schuichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.07.2016; Nature Publishing Group
• Subjects: 13/51; 14; 14/19; 14/28; 38/5; 38/77; 631/80/86/820; 692/4025/1334; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - secretion; Animals; ATP; Bladder; Cells, Cultured; Compliance; Exocytosis; Humanities and Social Sciences; Humans; Labeling; Localization; Male; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron, Transmission; multidisciplinary; Nucleotide Transport Proteins - genetics; Nucleotide Transport Proteins - metabolism; Science; Urinary Bladder - cytology; Urinary Bladder - metabolism; Urinary Bladder - ultrastructure; Urinary Tract - metabolism; Urination; Urine; Urothelium - cytology; Urothelium - metabolism; Urothelium - ultrastructure
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep29761

The bladder urothelium is more than just a barrier. When the bladder is distended, the urothelium functions as a sensor to initiate the voiding reflex, during which it releases ATP via multiple mechanisms. However, the mechanisms underlying this ATP release in response to the various stretch stimuli caused by bladder filling remain largely unknown. Therefore, the aim of this study was to elucidate these mechanisms. By comparing vesicular nucleotide transporter (VNUT)-deficient and wild-type male mice, we showed that ATP has a crucial role in urine storage through exocytosis via a VNUT-dependent mechanism. VNUT was abundantly expressed in the bladder urothelium and when the urothelium was weakly stimulated (i.e. in the early filling stages), it released ATP by exocytosis. VNUT-deficient mice showed reduced bladder compliance from the early storage phase and displayed frequent urination in inappropriate places without a change in voiding function. We conclude that urothelial, VNUT-dependent ATP exocytosis is involved in urine storage mechanisms that promote the relaxation of the bladder during the early stages of filling.