Title: Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis
Authors: Everaerts, Wouter *
Zhen, Xiaoguang *
Ghosh, Debapriya
Vriens, Joris
Gevaert, Thomas
Gilbert, James P
Hayward, Neil J
McNamara, Colleen R
Xue, Fenqin
Moran, Magdalene M
Strassmaier, Timothy
Uykal, Eda
Owsianik, Grzegorz
Vennekens, Rudi
De Ridder, Dirk
Nilius, Bernd
Fanger, Christopher M
Voets, Thomas # ×
Issue Date: 2-Nov-2010
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:107 issue:44 pages:19084-19089
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.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Urology Section (-)
Laboratory of Ion Channel Research
Screening, Diagnostics and Biomarkers (-)
Department of Cellular and Molecular Medicine - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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