title: Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria.
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.
authors.affiliation: Medway School of Pharmacy, Universities of Kent and Greenwich, Kent, United Kingdom.
authors.forename: Alberto
authors.initials: A
authors.lastname: Contreras-Sanz
authors.affiliation: Medway School of Pharmacy, Universities of Kent and Greenwich, Kent, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Krska
authors.affiliation: Obstetrics and Urogynaecology, Medway Maritime Hospital, Kent, United Kingdom.
authors.forename: Aswini A
authors.initials: AA
authors.lastname: Balachandran
authors.affiliation: Obstetrics and Urogynaecology, Medway Maritime Hospital, Kent, United Kingdom.
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Curtiss
authors.affiliation: Division of Medicine, UCL Medical School, London, United Kingdom.
authors.forename: Rajvinder
authors.initials: R
authors.lastname: Khasriya
authors.affiliation: Medway School of Pharmacy, Universities of Kent and Greenwich, Kent, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kelley
authors.affiliation: Department of Microbiology, East Kent Hospitals University Foundation Trust, Kent, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Strutt
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, London, United Kingdom.
authors.forename: Hardyal S
authors.initials: HS
authors.lastname: Gill
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, London, United Kingdom.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Taylor
authors.affiliation: School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia; and.
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: Mansfield
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Surrey, United Kingdom.
authors.forename: Changhao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Medway School of Pharmacy, Universities of Kent and Greenwich, Kent, United Kingdom.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Peppiatt-Wildman
authors.affiliation: Division of Medicine, UCL Medical School, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Malone-Lee
authors.affiliation: Obstetrics and Urogynaecology, Medway Maritime Hospital, Kent, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Duckett
authors.affiliation: Medway School of Pharmacy, Universities of Kent and Greenwich, Kent, United Kingdom; s.s.wildman@kent.ac.uk.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Wildman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002229:Carbenoxolone / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D011776:Pyuria / Q000150:complications / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058919:Purinergic P2 Receptor Antagonists; D013498:Suramin; D000255:Adenosine Triphosphate; D002229:Carbenoxolone; D014544:Uridine Triphosphate
keywords: ATP; overactive bladder; pyuria; urothelium