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TRPV4 receptor as a functional sensory molecule in bladder urothelium stretch-independent, tissue-specific actions and pathological implications

Roberts, MWG, Sui, G, Wu, R, Rong, W, Wildman, S, Montgomery, B, Ali, A, Langley, S, Ruggieri, M and Wu, C (2019) TRPV4 receptor as a functional sensory molecule in bladder urothelium stretch-independent, tissue-specific actions and pathological implications The FASEB Journal.

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Abstract

The newly-recognised sensory role of bladder urothelium has generated intense interest in identifying its novel sensory molecules. Sensory receptor TRPV4 may serve such function. However, specific and physiologically-relevant tissue actions of TRPV4, stretch-independent responses, and underlying mechanisms are unknown and its role in human conditions has not been examined. Here we showed TRPV4 expression in guinea-pig urothelium, suburothelium and bladder smooth muscle, with urothelial predominance. Selective TRPV4 activation without stretch evoked significant ATP release – key urothelial sensory process, from live mucosa tissue, full thickness bladder but not smooth muscle, and sustained muscle contractions. ATP release was mediated by Ca2+-dependent, pannexin/connexin-conductive pathway involving protein tyrosine kinase, but independent from vesicular transport and chloride channels. TRPV4 activation generated greater Ca2+ rise than purinergic activation in urothelial cells. There was intrinsic TRPV4 activity without exogeneous stimulus, causing ATP release. TRPV4 contributed to 50% stretch-induced ATP release. TRPV4 activation also triggered superoxide release. TRPV4 expression was increased with aging. Human bladder mucosa presented similarities to guinea-pigs. Overactive bladders exhibited greater TRPV4- induced ATP release with age-dependence. These data provide the first evidence in humans for the key functional role of TRPV4 in urothelium with specific mechanisms and identify TRPV4 upregulation in aging and overactive bladders.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Roberts, MWG
Sui, G
Wu, R
Rong, W
Wildman, S
Montgomery, B
Ali, A
Langley, S
Ruggieri, M
Wu, CC.Wu@surrey.ac.uk
Date : 2019
Funders : Biotechnology and Biological Sciences Research Council (BBSRC), Age UK, Henry Smith Charity
Copyright Disclaimer : © 2019 the Federation of American Societies for Experimental Biology
Uncontrolled Keywords : TRPV4 receptor; Urothelium; ATP release; Aging; Overactive bladders
Related URLs :
Depositing User : Clive Harris
Date Deposited : 01 Nov 2019 09:10
Last Modified : 15 Nov 2019 11:45
URI: http://epubs.surrey.ac.uk/id/eprint/853021

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