Are ATP, PG and NGF released from the urethral epithelium key mediator to develop overactive bladder?

尿道上皮释放的 ATP、PG 和 NGF 是导致膀胱过度活动症的关键介质吗？

• 批准号: 21659371
• 负责人: TANASE Kazuya
• 金额: $ 2.04万
• 依托单位: University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21659371/
• 关键词: 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

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

牵拉引起的尿道上皮释放某些介质可能在诱导混合性尿失禁或膀胱出口梗阻患者逼尿肌过度活动中起重要作用。在本研究中，我们评估尿道上皮是否能够合成和释放介质，以响应尿道扩张。尿道扩张3 min引起的ATP释放量显著增加，达到基线的13倍。PGE_2的释放也显著增加，是基线时的7倍。非选择性考克斯抑制剂酮洛芬显著抑制ATP释放64%和PGE_2释放51%。因此，有一种可能性，从尿道释放的介质参与逼尿肌过度活动的发展。EP 1拮抗剂ONO-8711和EP 3拮抗剂ONO-AE 5 -599均不影响PGE_2的释放。然而，它们显著抑制ATP释放。尿道内或 ...更多信息 静脉注射α_1受体阻滞剂坦索罗辛不抑制尿道ATP和PGE_2的释放，BOO大鼠尿道扩张引起的ATP释放量增加，达基线时的2倍。PGE_2的释放也增加，达到基线的6倍。与正常大鼠相比，BOO大鼠脑组织ATP释放明显减少。PGE_2的释放也有类似的趋势，但不显著。与正常大鼠相比，BOO大鼠脑组织ATP释放明显减少。PGE_2的释放也有类似的趋势，但无显著性差异。尿道内注射坦索罗辛不能抑制尿道上皮ATP或PGE_2释放的增加，虽然有报道α 1受体阻滞剂通过抑制尿道传入神经抑制逼尿肌过度活动，但其机制并不依赖于尿道尿道上皮的介质。考克斯抑制剂可减少尿激酶释放ATP，提示ATP与PGE_2之间存在相互作用。考克斯抑制剂可能成为治疗尿道功能不全引起的OAB的新策略。少

项目成果

Relationship between nocturia and metabolic syndrome

夜尿与代谢综合征的关系

• 发表时间: 2009
• 作者: Aoki Y;Kusukawa N;Matsuta Y;Maegawa M;Tanase K;Ito H;Oyama N;Miwa Y;Akino H;Yokoyama O
• 通讯作者: Yokoyama O

Epidemiology for men' s health

男性健康流行病学

• 发表时间: 2010
• 作者: Konno R;Yoshikawa H;et. al.;Yokoyama O
• 通讯作者: Yokoyama O

Selectiveα1A-blocker improves bladder storage function in rats via suppression of C-fiber afferent activity

选择性 α1A 阻滞剂通过抑制 C 纤维传入活动改善大鼠膀胱储存功能

• DOI: 10.1007/s00345-009-0481-2
• 发表时间: 2010
• 期刊: World J Urol
• 影响因子: 3.4
• 作者: Yokoyama O;Ito H;Aoki Y;Oyama N;Miwa Y;Akino H
• 通讯作者: Akino H

Zolpidem increases bladder capacity and decreases urine excretion in rats

唑吡坦增加大鼠膀胱容量并减少尿液排泄

• DOI: 10.1002/nau.20797
• 发表时间: 2010
• 期刊: Neurourol Urodyn
• 作者: Yokoyama O;Matsuta Y;Yanai-Inamura H;Watanabe M;Ohtake A;Suzuki M;Sasamata M
• 通讯作者: Sasamata M

Improvement of non-inflammatory detrusor overactivity through suppression of peripheral C-fiber by cyclooxygenase inhibitors

通过环氧合酶抑制剂抑制外周 C 纤维改善非炎症性逼尿肌过度活动

• 发表时间: 2010
• 期刊: J Urol 183
• 作者: Tanaka I;Nagase K;Tanase K;Aoki Y;Akino H;Yokoyama O.
• 通讯作者: Yokoyama O.