Alteration in TRPV1 and Muscarinic (M3) receptor expression and function in idiopathic overactive bladder urothelial cells.
Abstract
AIM
To examine function of both cholinergic (muscarinic) and TRPV1 receptors in human bladder urothelial (HBUC) from non-neurogenic
overactive bladder (OAB) patients as compared to control subjects.
METHODS
Primary HBUC cultures were derived from cystoscopic biopsies from OAB and control subjects. Muscarinic and TRPV1 function
was assessed by acetylcholine (5 μm) or capsaicin (0.5 μm) evoked ATP release, measured by luciferase assay. Overall, expression
of TRPV1 and muscarinic M3 receptors in bladder urothelial cells was accomplished using western immunoblotting.
RESULTS
Our findings revealed that the response to acetylcholine in OAB HBUC cultures (which was blocked by the nonselective muscarinic
antagonist, atropine methyl nitrate or AMN) was not significantly different than from controls. The acetylcholine M3 receptor
was slightly decreased as compared to control. In contrast, OAB HBUC cultures exhibited a capsaicin hypersensitivity and augmented
release of ATP (3.2 fold higher), which was blocked by the antagonist capsazepine. The increase in capsaicin sensitivity correlated
with increased urothelial TRPV1 expression.
CONCLUSION
Though characterized in a small number of subjects, augmented release of urothelial-derived transmitters such as ATP could
'amplify' signalling between and within urothelial cells and nearby afferent nerves.
Links
Authors
Birder LA, Wolf-Johnston AS, Sun Y, Chai TC
Institution
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. lbirder@pitt.edu
Source
Acta physiologica (Oxford, England) 207:1 2013 Jan pg 123-9Pub Type(s)
Journal ArticleResearch Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Language
eng
PubMed ID
22691178
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