Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome.

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Version: Author's accepted manuscript
Serval ID
serval:BIB_9046470460E6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome.
Journal
Journal of Urology
Author(s)
Sánchez-Freire V., Blanchard M.G., Burkhard F.C., Kessler T.M., Kellenberger S., Monastyrskaya K.
ISSN
1527-3792 (Electronic)
ISSN-L
0022-5347
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
186
Number
4
Pages
1509-1516
Language
english
Abstract
Purpose: To examine the possible role of H+-activated acid-sensing ion channels (ASICs) in pain perception we characterized their expression in bladder dome biopsies of Bladder Pain Syndrome (BPS) patients and controls, in cultured human urothelium and in urothelial TEU-2 cells.Materials and Methods: Cold cut biopsies from the bladder dome were obtained in 8 asymptomatic controls and 28 patients with symptoms of BPS. ASIC expression was analyzed by QPCR and immunofluorescence. The channel function was measured by electrophysiology.Results: ASIC1a, ASIC2a and ASIC3 mRNAs were detected in human bladder. Similar amounts of ASIC1a and -3 were detected in detrusor smooth muscle, whereas in urothelium ASIC3 levels were higher than -1a. ASIC2a mRNA levels were lower than either -1a or -3 in both layers. ASIC currents were measured in TEU-2 cells and in primary cultures of human urothelium, and ASIC expression was confirmed by QPCR. Differentiation of TEU-2 cells caused an up-regulation of ASIC2a and ASIC3, and a down-regulation of ASIC1a mRNAs. BPS patients showed an up-regulation of ASIC2a and -3 mRNA, whereas ASIC1a remained unchanged. In contrast, the mRNA levels of TRPV1 were down-regulated during BPS. All differences were statistically significant (p<0.05)Conclusions: Several different ASIC subunits are expressed in human bladder and TEU-2 cells, where their levels are regulated during urothelial differentiation. An up-regulation of ASIC2a and -3 in BPS suggests their involvement in increased pain and hyperalgesia. A down-regulation of TRPV1 mRNA levels might indicate a different regulatory mechanism, controlling its expression in human bladder.
Keywords
Aged, Amiloride/pharmacology, Capsaicin/pharmacology, Cell Line, Cells, Cultured, Cystitis, Interstitial/metabolism, Cystitis, Interstitial/physiopathology, Electrophysiological Phenomena/drug effects, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Tissue Proteins/metabolism, Patch-Clamp Techniques, Sodium Channels/metabolism, TRPV Cation Channels/metabolism, Urinary Bladder/metabolism, Urothelium/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
03/05/2011 7:19
Last modification date
20/10/2020 14:41
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