title: Serotonergic regulation of distention-induced ATP release from the urothelium.
abstract: Serotonin [5-hydroxytryptamine (5-HT)] is involved in both motor and sensory functions in hollow organs, especially in the gastrointestinal tract. However, the involvement of 5-HT in visceral sensation of the urinary bladder remains unknown. Because distention-induced ATP release from the urothelium plays an essential role in visceral sensation of the urinary bladder, we investigated the regulation of urothelial ATP release by the 5-HT signaling system. RT-PCR and immunohistochemical analyses of the urothelium revealed specific expression of 5-HT1Dand 5-HT4receptors. The addition of 5-HT did not affect urothelial ATP release without bladder distention, but it significantly reduced distention-induced ATP release by physiological pressure during urine storage (5 cmH2O). The inhibitory effect of 5-HT on distention-elicited ATP release was blocked by preincubation with the 5-HT1B/1Dantagonist GR-127935 but not by the 5-HT4antagonist SB-204070. mRNA encoding tryptophan hydroxylase 1 was detected in the urinary bladder by nested RT-PCR amplification, and l-tryptophan or the selective serotonin reuptake inhibitor citalopram also inhibited ATP release, indicating that 5-HT is endogenously synthesized and released in the urinary bladder. The addition of GR-127935 significantly enhanced the distention-elicited ATP release 40 min after distention, whereas SB-204070 reduced the amount of ATP release 20 min after distention. These data suggest that 5-HT4facilitates the distention-induced ATP release at an earlier stage, whereas 5-HT1Dinhibits ATP release at a later stage. The net inhibitory effect of 5-HT indicates that the action of 5-HT on the urothelium is mediated predominantly by 5-HT1D.
authors.affiliation: Department of Neurophysiology, Akita University Graduate School of Medicine, Akita, Japan; ka-miyai@zf7.so-net.ne.jp.|Kansai University of Nursing and Health Sciences, Hyogo, Japan; and.|Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto-Miyai
authors.affiliation: Department of Neurophysiology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Yamada
authors.affiliation: Department of Neurophysiology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Shinzawa
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Department of Neurophysiology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshizumi
authors.affiliation: Department of Neurophysiology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kawatani
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015283:Citalopram / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D015283:Citalopram; D004146:Dioxanes; D010069:Oxadiazoles; D010879:Piperazines; D010880:Piperidines; D044346:Receptor, Serotonin, 5-HT1D; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C084858:SB 204070A; C090701:GR 127935
keywords: 5-hydroxytryptamine; 5-hydroxytryptamine1D; 5-hydroxytryptamine4; urinary bladder; urine storage