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Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Contreras-Sanz, Alberto, Krska, Louise, Balachandran, Aswini A., Curtiss, Natasha L., Khasriya, Rajvinder, Kelley, Stephen P., Strutt, Matthew, Gill, Hardyal S., Taylor, Kevin, Mansfield, Kylie J., and others. (2016) Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria. American Journal of Physiology. Renal physiology, 311 (4). F805-F816. ISSN 1931-857X. (doi:10.1152/ajprenal.00339.2015)

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http://dx.doi.org/10.1152/ajprenal.00339.2015

Abstract

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (?10 wbc/?l) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/?l). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ?80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients.

Item Type: Article
DOI/Identification number: 10.1152/ajprenal.00339.2015
Uncontrolled keywords: ATP; overactive bladder; pyuria; urothelium
Subjects: Q Science
Q Science > QP Physiology (Living systems)
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Rebecca Brown
Date Deposited: 15 Dec 2016 11:33 UTC
Last Modified: 29 May 2019 18:29 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/59718 (The current URI for this page, for reference purposes)
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