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首页> 外文期刊>American Journal of Physiology >TRPV4 blockade reduces voiding frequency, ATP release, and pelvic sensitivity in mice with chronic urothelial overexpression of NGF.
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TRPV4 blockade reduces voiding frequency, ATP release, and pelvic sensitivity in mice with chronic urothelial overexpression of NGF.

机译：TRPV4封锁降低了慢性尿路上皮过表达NGF的小鼠中的空隙频率，ATP释放和盆腔敏感性。

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摘要

Transient receptor potential vanilloid family member 4 (TRPV4) transcript and protein expression increased in the urinary bladder and lumbosacral dorsal root ganglia of transgenic mice with chronic urothelial over-expression of nerve growth factor (NGF-OE). We evaluated the functional role of TRPV4 in bladder function with open-outlet cys-lometry, void spot assays, and natural voiding (Urovoid) assays with the TRPV4 antagonist HC-067047 (1 muM) or vehicle in NGF-OE and littermate wild-type (WT) mice. Blockade of TRPV4 at the level of the urinary bladder significantly (P S 0.01) increased the intercon-traction interval (2.2-fold) and void volume (2.6-fold) and decreased nonvoiding contractions (3.0-fold) in NGF-OE mice, with lesser effects (1.3-fold increase in the intercontraction interval and 13-fold increase in the void volume) in WT mice. Similar effects of TRPV4 blockade on bladder function in NGF-OE mice were demonstrated with natural voiding assays. Intravesical administration of HC-067047 (1 muM) significantly (P < 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in littermate WT mice. Blockade of urinary bladder TRPV4 or intravesical infusion of brefeldin A significantly (P < 0.01) reduced (2-fold) luminal ATP release from the urinary bladder in NGF-OE and littermate WT mice. The results of the present study suggest that TRPV4 contributes to luminal ATP release from the urinary bladder and increased voiding frequency and pelvic sensitivity in NGF-OE mice.
机译：瞬态受体潜在的香草族家族构件4（TRPV4）转录物和蛋白质表达在膀胱和腰骶部的转基因小鼠的膀胱和腰骶部神经节中增加了神经生长因子（NGF-OE）的转基因小鼠的肺肺部背根神经节。我们评估了TRPV4在NGF-OE中的TRPV4拮抗剂HC-067047（1妈妈）和缺血件中的膀胱函数，空隙点测定和天然空隙（核素）测定的功能作用。类型（wt）小鼠。在尿膀胱水平下阻断TRPV4显着（PS 0.01）增加了互连间隔（2.2倍）和空隙体积（2.6倍），并且在NGF-OE小鼠中降低了非翻斗收缩（3.0倍），在WT小鼠中，效果较小的效果（12倍的间歇间隔和空隙体积增加13倍）。 TRPV4嵌段对NGF-OE小鼠膀胱功能的类似效果，用天然空隙测定证明了。 HC-067047（1毫米）的膀胱内施用显着（P <0.01）降低了NGF-OE小鼠中的盆腔敏感性，但没有效果在凋落物WT小鼠中。膀胱膀胱Trpv4或Brefeldin的膀胱内输注显着（P <0.01）从NGF-OE和凋落物WT小鼠中从膀胱减少（2倍）腔内ATP释放。本研究的结果表明，TRPV4从膀胱释放到尿膀胱和NGF-OE小鼠中的空隙频率和盆腔敏感性增加。

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