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

Contreras-Sanz, A; Krska, L; Balachandran, AA; Curtiss, NL; Khasriya, R; Kelley, S; Strutt, M; ... Wildman, SS; + view all (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. 10.1152/ajprenal.00339.2015. Green open access

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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/μl) 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/μl). 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.

Type: Article
Title: Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajprenal.00339.2015
Publisher version: http://dx.doi.org/10.1152/ajprenal.00339.2015
Language: English
Additional information: Copyright © 2016 the American Physiological Society.
Keywords: ATP, overactive bladder, pyuria, urothelium
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Nephrology
URI: http://discovery.ucl.ac.uk/id/eprint/1502331
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