{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:39:12Z","timestamp":1783633152543,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2019,10,13]],"date-time":"2019-10-13T00:00:00Z","timestamp":1570924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Functional disorders (i.e. interstitial cystitis\/painful bladder syndrome and irritable bowel syndrome) are associated with hyperexcitability of afferent nerves innervating the urinary tract and the bowel, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Various non\u20105\u2010HT<jats:sub>3<\/jats:sub> receptor mRNA transcripts are expressed in mouse urothelium and exert functional responses to 5\u2010HT.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Whilst 5\u2010HT<jats:sub>3<\/jats:sub> receptors were not detected in mouse urothelium, 5\u2010HT<jats:sub>3<\/jats:sub> receptors expressed on bladder sensory neurons plays a role in bladder afferent excitability both under normal conditions and in a mouse model of chronic visceral hypersensitivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data suggest that the role 5\u2010HT<jats:sub>3<\/jats:sub> receptors play in bladder afferent signalling warrants further study as a potential therapeutic target for functional bladder disorders.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Serotonin (5\u2010HT) is an excitatory mediator that in the gastrointestinal (GI) tract plays a physiological role in gut\u2013brain signalling and is dysregulated in functional GI disorders such as irritable bowel syndrome (IBS). Patients suffering from IBS frequently suffer from urological symptoms characteristic of interstitial cystitis\/painful bladder syndrome, which manifests due to cross\u2010sensitization of shared innervation pathways between the bladder and colon. However, a direct modulatory role of 5\u2010HT in bladder afferent signalling and its role in colon\u2013bladder neuronal crosstalk remain elusive. The aim of this study was to investigate the action of 5\u2010HT on bladder afferent signalling in normal mice and mice with chronic visceral hypersensitivity (CVH) following trinitrobenzenesulfonic acid\u2010induced colitis. Bladder afferent activity was recorded directly using <jats:italic>ex vivo<\/jats:italic> afferent nerve recordings. Expression of 14 5\u2010HT receptor subtypes, the serotonin transporter (SERT) and 5\u2010HT\u2010producing enzymes was determined in the urothelium using RT\u2010PCR. Retrograde labelling of bladder\u2010projecting dorsal root ganglion neurons was used to investigate expression of 5\u2010HT<jats:sub>3<\/jats:sub> receptors using single cell RT\u2010PCR, while sensory neuronal and urothelial responses to 5\u2010HT were determined by live cell calcium imaging. 5\u2010HT elicited bladder afferent firing predominantly via 5\u2010HT<jats:sub>3<\/jats:sub> receptors expressed on afferent terminals. CVH animals showed a downregulation of SERT mRNA expression in urothelium, suggesting increased 5\u2010HT bioavailability. Granisetron, a 5\u2010HT<jats:sub>3<\/jats:sub> antagonist, reversed bladder afferent hypersensitivity in CVH mice. These data suggest 5\u2010HT exerts a direct effect on bladder afferents to enhance signalling. 5\u2010HT<jats:sub>3<\/jats:sub> antagonists could therefore be a potential therapeutic target to treat functional bladder and bowel disorders.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278751","type":"journal-article","created":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T12:54:27Z","timestamp":1568465667000},"page":"5247-5264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Serotonin exerts a direct modulatory role on bladder afferent firing in mice"],"prefix":"10.1113","volume":"597","author":[{"given":"N.","family":"Konthapakdee","sequence":"first","affiliation":[{"name":"Department of Physiology Faculty of Science Prince of Songkla University  Hat Yai Songkhla 90112 Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Grundy","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group Centre for Neuroscience College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Hopwood Centre for Neurobiology Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  North Terrace Adelaide South Australia 5000 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases Discipline of Medicine University of Adelaide  North Terrace Adelaide South Australia 5000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group Centre for Neuroscience College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Hopwood Centre for Neurobiology Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  North Terrace Adelaide South Australia 5000 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases Discipline of Medicine University of Adelaide  North Terrace Adelaide South Australia 5000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Garcia\u2010Caraballo","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group Centre for Neuroscience College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Hopwood Centre for Neurobiology Lifelong Health Theme South Australian Health and Medical Research Institute (SAHMRI)  North Terrace Adelaide South Australia 5000 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases Discipline of Medicine University of Adelaide  North Terrace Adelaide South Australia 5000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-2905","authenticated-orcid":false,"given":"S. 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