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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 Tdoi
10.1073/pnas.1005333107subject
Has Abstractpub_date
2010-11-02 00:00:00pages
19084-9issue
44eissn
0027-8424issn
1091-6490pii
1005333107journal_volume
107pub_type
杂志文章abstract::Purified RNA polymerase II (pol II) from the yeast Saccharomyces cerevisiae pauses without releasing at many locations during in vitro transcription. Pausing can be induced by intrinsic DNA sequence as well as by specific DNA bound proteins such as the RNA pol I termination factor, Reb1p, or lac repressor. Addition of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1980-03-01 00:00:00