{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:03:31Z","timestamp":1792674211826,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2016,4,24]],"date-time":"2016-04-24T00:00:00Z","timestamp":1461456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The sensory components of the urinary bladder are responsible for the transduction of bladder filling and are often impaired with neurological injury or disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Elevated extracellular ATP contributes, in part, to bladder afferent nerve hyperexcitability during urinary bladder inflammation or irritation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) may stimulate ATP release from the urothelium through vesicular exocytosis mechanisms with minimal contribution from pannexin\u20101 channels to increase bladder afferent nerve discharge.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Bladder afferent nerve hyperexcitability and urothelial ATP release with CYP\u2010induced cystitis is decreased with TGF\u2010\u03b2 inhibition.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results establish a causal link between an inflammatory mediator, TGF\u2010\u03b2, and intrinsic signalling mechanisms of the urothelium that may contribute to the altered sensory processing of bladder filling.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The afferent limb of the micturition reflex is often compromised following bladder injury, disease and inflammatory conditions. We have previously demonstrated that transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signalling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Despite the functional presence of TGF\u2010\u03b2 in bladder inflammation, the precise mechanisms of TGF\u2010\u03b2 mediating bladder dysfunction are not yet known. Thus, the present studies investigated the sensory components of the urinary bladder that may underlie the pathophysiology of aberrant TGF\u2010\u03b2 activation. We utilized bladder\u2013pelvic nerve preparations to characterize bladder afferent nerve discharge and the mechanisms of urothelial ATP release with distention. Our findings indicate that bladder afferent nerve discharge is sensitive to elevated extracellular ATP during pathological conditions of urinary bladder inflammation or irritation. We determined that TGF\u2010\u03b21 may increase bladder afferent nerve excitability by stimulating ATP release from the urothelium via vesicular exocytosis mechanisms with minimal contribution from pannexin\u20101 channels. Furthermore, blocking aberrant TGF\u2010\u03b2 signalling in cyclophosphamide\u2010induced cystitis with T\u03b2R\u20101 inhibition decreased afferent nerve hyperexcitability with a concomitant decrease in urothelial ATP release. Taken together, these results establish a role for purinergic signalling mechanisms in TGF\u2010\u03b2\u2010mediated bladder afferent nerve activation that may ultimately facilitate increased voiding frequency. The synergy between intrinsic urinary bladder signalling mechanisms and an inflammatory mediator provides novel insight into bladder dysfunction and supports new avenues for therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272148","type":"journal-article","created":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T08:27:18Z","timestamp":1458721638000},"page":"3575-3588","source":"Crossref","is-referenced-by-count":21,"title":["Purinergic signalling underlies transforming growth factor\u2010\u03b2\u2010mediated bladder afferent nerve hyperexcitability"],"prefix":"10.1113","volume":"594","author":[{"given":"Eric J.","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences University of Vermont College of Medicine  Burlington VT 05405 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Heppner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Vermont 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