title: Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase.
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.
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagomi
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Yoshiyama
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mochizuki
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Komatsu
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Imura
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Morizawa
authors.affiliation: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Density, and Pharmaceutical Science, Okayama 700-8530, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hiasa
authors.affiliation: Advanced Science Research Center, Okayama University, Okayama 700-8530, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Miyaji
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kira
authors.affiliation: Department of Urology, Shiga University of Medical Science, Shiga 520-2192, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Araki
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Fujishita
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.|Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.|Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shigetomi
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.|Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Shinozaki
authors.affiliation: Institute of Life Sciences, Ajinomoto Co. Inc., Kawasaki 210-8681, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ichikawa
authors.affiliation: Institute of Life Sciences, Ajinomoto Co. Inc., Kawasaki 210-8681, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Uneyama
authors.affiliation: Institute of Life Sciences, Ajinomoto Co. Inc., Kawasaki 210-8681, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Iwatsuki
authors.affiliation: Department of Endocrine and Metabolic Diseases/Diabetes Mellitus Kyushu University Hospital, Fukuoka 812-8582, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.affiliation: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Density, and Pharmaceutical Science, Okayama 700-8530, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Moriyama
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.|Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
authors.forename: Schuichi
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005089:Exocytosis; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D033704:Nucleotide Transport Proteins / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D014551:Urinary Tract / Q000378:metabolism; D014554:Urination; D019459:Urothelium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D033704:Nucleotide Transport Proteins; C578984:Slc17a9 protein, mouse; D000255:Adenosine Triphosphate