{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T18:19:03Z","timestamp":1778350743079,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>It is now well established that the urothelium does not act as a passive barrier but contributes to bladder homeostasis by releasing several signaling molecules in response to physiological and chemical stimuli. Here, we investigated the potential contribution of the hydrogen sulfide (H2S) pathway in regulating human urothelium function in \u03b23 adrenoceptor-mediated relaxation. The relaxant effect of BRL 37344 (0.1\u2013300 \u00b5M), a selective \u03b23 adrenoceptor agonist, was evaluated in isolated human bladder strips in the presence or absence of the urothelium. The relaxant effect of BRL 37344 was significantly reduced by urothelium removal. The inhibition of cystathionine-\u03b3-lyase (CSE), but not cystathionine-\u03b2-synthase (CBS), significantly reduced the BRL 37344 relaxing effect to the same extent as that given by urothelium removal, suggesting a role for CSE-derived H2S. \u03b23 adrenoceptor stimulation in the human urothelium or in T24 urothelial cells markedly increased H2S and cAMP levels that were reverted by a blockade of CSE and \u03b23 adrenoceptor antagonism. These findings demonstrate a key role for urothelium CSE-derived H2S in the \u03b23 effect on the human bladder through the modulation of cAMP levels. Therefore, the study establishes the relevance of urothelial \u03b23 adrenoceptors in the regulation of bladder tone, supporting the use of \u03b23 agonists in patients affected by an overactive bladder.<\/jats:p>","DOI":"10.3390\/antiox11081480","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"1480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u03b23 Relaxant Effect in Human Bladder Involves Cystathionine \u03b3-Lyase-Derived Urothelial Hydrogen Sulfide"],"prefix":"10.3390","volume":"11","author":[{"given":"Emma","family":"Mitidieri","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"},{"name":"Interdepartmental Centre for Sexual Medicine, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Pecoraro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0063-659X","authenticated-orcid":false,"given":"Vincenzo","family":"Brancaleone","sequence":"additional","affiliation":[{"name":"Department of Science, University of Basilicata, 85100 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Turnaturi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Mirone","sequence":"additional","affiliation":[{"name":"Interdepartmental Centre for Sexual Medicine, University of Naples Federico II, 80131 Naples, Italy"},{"name":"Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, Urology Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Cirino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"},{"name":"Interdepartmental Centre for Sexual Medicine, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-5424","authenticated-orcid":false,"given":"Raffaella","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Interdepartmental Centre for Sexual Medicine, University of Naples Federico II, 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3891-3350","authenticated-orcid":false,"given":"Giulia","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7509-3702","authenticated-orcid":false,"given":"Annapina","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"d\u2019Emmanuele di Villa Bianca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"},{"name":"Interdepartmental Centre for Sexual Medicine, 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