| Project/Area Number |
21659371
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | University of Fukui |
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Principal Investigator |
TANASE Kazuya 福井大学, 医学部・附属病院, 助教 (00359720)
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| Co-Investigator(Kenkyū-buntansha) |
AKINO Hironobu 福井大学, 医学部, 准教授 (90159335)
YOKOYAMA Osamu 福井大学, 医学部, 教授 (90242552)
KUSUKAWA Naoya 福井大学, 医学部, 助教 (80372499)
WATANABE Nozomu 福井大学, 医学部附属病院, 医員 (80572429)
松田 陽介 福井大学, 医学部, 助教 (90345687)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,180,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2009: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | 前立腺肥大症 / 混合性尿失禁 / 尿道上皮 / ATP / Prostaglandin / α_1遮断薬 / COX inhibitor / EP遮断薬 / 過活動膀胱 / 尿道 / 上皮細胞 / 知覚神経 / prostaglandin / 下部尿路 / mediator |
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| Research Abstract |
Stretch-induced release of some mediators from the urethral epithelium may play an important role in the induction of detrusor overactivity in patients with mixed incontinence or bladder outlet obstruction. In the present study, we evaluated whether the urethral epithelium was capable of synthesizing and releasing mediators in response to urethral distension. The ATP releases elicited by urethral distension for three minutes increased significantly, reaching13 times as much as those at baseline. The PGE_2 release also increased significantly, 7 times as much as those at baseline. The nonselective COX inhibitor ketoprofen significantly suppressed ATP release by 64% and PGE_2 release by 51%. Therefore, there is a possibility that mediators released from the urethra participate in the development of detrusor overactivity. PGE_2 release was not influented by both of EP1 antagonist ONO-8711 or EP3 antagonist ONO-AE5-599. However they significantly suppressed ATP release. Intraurethral or in
… More
travenous administration of a1-blocker tamsulosin did not suppress ATP or PGE_2 release from the urethra.
In BOO rats ; the ATP release elicited by urethral distension increased reaching 2 times as much as those at baseline. The PGE_2 release also increased reaching 6 times as much as those at baseline. As compared with the normal rats, the ATP release of BOO rats were decreased significantly. A similar trend was observed for the PGE_2 release, but not significantly. As compared with the normal rats, the ATP release of BOO rats were significantly decreased. A similar trend was observed for the PGE_2 release, but without significance. Intraurethral administration of tamsulosin did not suppress the increase in ATP or PGE_2 release from the urethral epithelium.
Although a1-blocker has been reported to suppress detrusor overactivity via inhibition of urethral afferent nerves, the underlying mechanism did not depend on mediators from the urethral urothelium. COX inhibitors decreased ATP release from the urethelium, suggesting that there was an interaction between ATP and PGE_2. COX inhibitors may become a new therapeutic strategy for patients with OAB caused by the incompetent urethra. Less
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