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

Hiroshi Nakagomi, Mitsuharu Yoshiyama, Tsutomu Mochizuki, Tatsuya Miyamoto, Ryohei Komatsu, Yoshio Imura, Yosuke Morizawa, Miki Hiasa, Takaaki Miyaji, Satoru Kira, Isao Araki, Kayoko Fujishita, Keisuke Shibata, Eiji Shigetomi, Youichi Shinozaki, Reiko Ichikawa, Hisayuki Uneyama, Ken Iwatsuki, Masatoshi Nomura, William C. De GroatYoshinori Moriyama, Masayuki Takeda, Schuichi Koizumi

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Abstract

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.

Original languageEnglish
Article number29761
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Jul 14 2016

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Nakagomi, H., Yoshiyama, M., Mochizuki, T., Miyamoto, T., Komatsu, R., Imura, Y., ... Koizumi, S. (2016). Urothelial ATP exocytosis: Regulation of bladder compliance in the urine storage phase. Scientific reports, 6, [29761]. https://doi.org/10.1038/srep29761