Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.

Abstract:

: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.

authors

Everaerts W,Zhen X,Ghosh D,Vriens J,Gevaert T,Gilbert JP,Hayward NJ,McNamara CR,Xue F,Moran MM,Strassmaier T,Uykal E,Owsianik G,Vennekens R,De Ridder D,Nilius B,Fanger CM,Voets T

doi

10.1073/pnas.1005333107

subject

Has Abstract

pub_date

2010-11-02 00:00:00

pages

19084-9

issue

44

eissn

0027-8424

issn

1091-6490

pii

1005333107

journal_volume

107

pub_type

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