TRPV4型
排尿
膀胱过度活动
下尿路症状
增生
医学
尿路上皮
泌尿科
膀胱
环磷酰胺
泌尿系统
内科学
内分泌学
瞬时受体电位通道
前列腺
病理
化疗
受体
替代医学
癌症
作者
Wouter Everaerts,Xiao-guang Zhen,Debapriya Ghosh,Joris Vriens,Thomas Gevaert,James P. Gilbert,Neil J. Hayward,Colleen R. McNamara,Fenqin Xue,Magdalene M. Moran,Timothy Strassmaier,Eda Uykal,Grzegorz Owsianik,Rudi Vennekens,Dirk De Ridder,Bernd Nilius,Christopher M. Fanger,Thomas Voets
标识
DOI:10.1073/pnas.1005333107
摘要
Reduced functional bladder capacity and concomitant increased micturition frequency (pollakisuria) are common lower urinary tract symptoms associated with conditions such as cystitis, prostatic hyperplasia, neurological disease, and overactive bladder syndrome. These symptoms can profoundly affect the quality of life of afflicted individuals, but available pharmacological treatments are often unsatisfactory. Recent work has demonstrated that the cation channel TRPV4 is highly expressed in urothelial cells and plays a role in sensing the normal filling state of the bladder. In this article, we show that the development of cystitis-induced bladder dysfunction is strongly impaired in Trpv4(-/-) mice. Moreover, we describe HC-067047, a previously uncharacterized, potent, and selective TRPV4 antagonist that increases functional bladder capacity and reduces micturition frequency in WT mice and rats with cystitis. HC-067047 did not affect bladder function in Trpv4(-/-) mice, demonstrating that its in vivo effects are on target. These results indicate that TRPV4 antagonists may provide a promising means of treating bladder dysfunction.
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