| 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)
古谷 泰久 山梨大学, 医学部附属病院, 助手 (10238701)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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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 / Epithelial Sodium Channel / Urinary Bladder / Bladder Outlet Obstruction / Mechanosensory Transduction / Overactive Bladder |
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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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