2005 Fiscal Year Final Research Report Summary
Role of ENaC/Deg.Channel Family in Afferent Transduction of Lower Urinary Tract.
| Project/Area Number |
16591588
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
ARAKI Isao University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Associate Professor, 大学院・医学工学総合研究部, 助教授 (50252424)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Masayuki University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院・医学工学総合研究部, 教授 (80197318)
FUKASAWA Mizuya University of Yamanashi, University of Yamanashi Hospital, Assistant Professor, 医学部附属病院, 講師 (80252039)
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| Project Period (FY) |
2004 – 2005
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| Keywords | amiloride-sensitive sodium channel / epithelial Na^+ channel / micturition reflex / bladder outlet obstruction / afferent function / ATP / bladder epithelium / mechano-sensory transduction |
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| Research Abstract |
1. ENaC expression in the human urinary bladder :
The expression of each ENaC subunit (α, β and γ) was extremely poor in normal bladders. However, the expression levels of each ENaC subunit in the bladder epithelium were significantly increased in human obstructed bladders. The quantified ENaC expression in the epithelium was significantly correlated with storage symptom score.
2. ENaC expression in the rat urinary bladder :
All ENaC subunit (α, β and γ) proteins and genes were clearly detected in the rat normal bladder epithelium. Thus, ENaC expression in the bladder epithelium showed a remarkable species difference between the rat and human. In double immunofluoresent staining of rat bladder mucosa with anti-CGRP antibodies, only a small part of CGRP-immunoreactive sensory nerve terminals co-expressed ENaC.
3. Role of ENaC in micturition reflex :
In cystometry with continuous saline infusion, the intravesical perfusion of 1mM amiloride significantly reduced the frequency of reflex voiding
… More
during bladder filling. This effect of amiloride was reversible by washing out the drug. The peak amplitude of micturition pressure was not affected by amiloride.
4. Role of ENaC in stretch-evoked ATP release from bladder epithelium :
Bladder strips with or without epithelium suspended in organ bath were subjected to varying degrees of mechanical stretch. Using luciferine-luciferase assay, we found that the stretch-evoked ATP release, a majority of which (over 90%) came from epithelial layer, was greatly diminished by 1mM amiloride (from 443 to 22% increase from basal level at 50% stretch of original length).
These findings indicate that the amiloride-sensitive sodium channels expressed in the rat bladder epithelium participate in the mechanosensory transduction mechanism by controlling stretch-evoked ATP release. The increased ENaC expression in the human bladder epithelium might change the afferent activity, which is involved in the induction of detrusor instability due to bladder outlet obstruction. Less
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Research Products
(41 results)
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[Journal Article] Human muscarinic receptor binding characteristics of antimuscarinic agents totreat overactive bladder.2006
Author(s)
S Maruyama, T Oki, A Otsuka, H Shinbo, S Ozono, S Kageyama, Y Mikami, I Araki, M Takeda, K Masuyama, S Yamada
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Journal Title
Journal of Urology 175
Pages: 365-369
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Human muscarinic receptor binding characteristics of antimuscarinic agents to treat overactive bladder.2006
Author(s)
S Maruyama, T Oki, A Otsuka, H Shinbo, S Ozono, S Kageyama, Y Mikami, I Araki, M Takeda, K Masuyama, S Yamada
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Journal Title
Journal of Urology 175
Pages: 365-369
Description
「研究成果報告書概要(欧文)」より
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[Book] 過活動膀胱診療ガイドライン(日本排尿機能学会過活動膀胱ガイドライン作成委員会編集)pp.57-65、、東京、2005.8.30.2005
Author(s)
柿崎秀宏, 井川靖彦, 後藤百万, 武田正之, 長谷川友紀, 小柳知彦, 荒木勇雄, 石塚修, 加藤久美子, 木元康介, 佐藤智哉, 柴田隆, 田中博, 前澤浩明, 吉川羊子
Total Pages
84
Publisher
Blackwell Publishing社
Description
「研究成果報告書概要(和文)」より
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