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Altered Urothelial ATP Signaling in Major Subset of Human Overactive Bladder Patients with Pyuria

Contreras-Sanz, A, Krska, L, Balachandran, AA, Curtiss, NL, Khasriya, R, Kelley, S, Strutt, M, Gill, HS, Taylor, KM, Mansfield, KJ, Wu, C, Peppiatt-Wildman, CM, Malone-Lee, J, Duckett, J and Wildman, SS (2016) Altered Urothelial ATP Signaling in Major Subset of Human Overactive Bladder Patients with Pyuria American Journal of Physiology Renal, 311 (4). F805-F816.

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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-1) 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 urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc μl -1). Basal ATP release from 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 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
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
AuthorsEmailORCID
Contreras-Sanz, AUNSPECIFIEDUNSPECIFIED
Krska, LUNSPECIFIEDUNSPECIFIED
Balachandran, AAUNSPECIFIEDUNSPECIFIED
Curtiss, NLUNSPECIFIEDUNSPECIFIED
Khasriya, RUNSPECIFIEDUNSPECIFIED
Kelley, SUNSPECIFIEDUNSPECIFIED
Strutt, MUNSPECIFIEDUNSPECIFIED
Gill, HSUNSPECIFIEDUNSPECIFIED
Taylor, KMUNSPECIFIEDUNSPECIFIED
Mansfield, KJUNSPECIFIEDUNSPECIFIED
Wu, CUNSPECIFIEDUNSPECIFIED
Peppiatt-Wildman, CMUNSPECIFIEDUNSPECIFIED
Malone-Lee, JUNSPECIFIEDUNSPECIFIED
Duckett, JUNSPECIFIEDUNSPECIFIED
Wildman, SSUNSPECIFIEDUNSPECIFIED
Date : 29 June 2016
Identification Number : 10.1152/ajprenal.00339.2015
Copyright Disclaimer : Copyright © 2015, American Journal of Physiology - Renal Physiology
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 29 Jun 2016 17:40
Last Modified : 22 Nov 2016 15:34
URI: http://epubs.surrey.ac.uk/id/eprint/811078

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