title: Authentic role of ATP signaling in micturition reflex.
abstract: Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2(-/-) and P2X3(-/-) mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex.
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.|Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takezawa
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiuchi
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Norichika
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Soda
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takao
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto-Miyai
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Negoro
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Shimada
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D058476:Receptors, Purinergic P2X2 / Q000172:deficiency / Q000378:metabolism; D058477:Receptors, Purinergic P2X3 / Q000172:deficiency / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014554:Urination / Q000187:drug effects / Q000502:physiology*; D014563:Urodynamics / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate