Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/122497
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Serotonin exerts a direct modulatory role on bladder afferent firing in mice
Author: Konthapakdee, N.
Grundy, L.
O'Donnell, T.
Garcia-Caraballo, S.
Brierley, S.M.
Grundy, D.
Daly, D.M.
Citation: The Journal of Physiology, 2019; 597(21):5247-5264
Publisher: Wiley
Issue Date: 2019
ISSN: 0022-3751
1469-7793
Statement of
Responsibility: 
N. Konthapakdee, L. Grundy T. O'Donnell, S. Garcia-Caraballo, S. M. Brierley, D. Grundy, D. M. Daly
Abstract: KEY POINTS: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. Various non-5-HT3 receptor mRNA transcripts are expressed in mouse urothelium and exert functional responses to 5-HT. Whilst 5-HT3 receptors were not detected in mouse urothelium, 5-HT3 receptors expressed on bladder sensory neurons plays a role in bladder afferent excitability under both normal conditions and in a mouse model of chronic visceral hypersensitivity (CVH). These data suggest that the role 5-HT3 receptors play in bladder afferent signaling warrants further study as a potential therapeutic target for functional bladder disorders. ABSTRACT:Serotonin (5-HT) is an excitatory mediator, which in the gastrointestinal (GI) tract, plays a physiological role in gut-brain signaling and which 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-sensitization of shared innervation pathways between the bladder and colon. However, a direct modulatory role of 5-HT in bladder afferent signaling and its role in colon-bladder neuronal crosstalk remain elusive. The aim of this study was to investigate the action of 5-HT on bladder afferent signaling in normal mice and mice with chronic visceral hypersensitivity (CVH) following trinitrobenzenesulfonic acid (TNBS) induced colitis. Bladder afferent activity was recorded directly using ex vivo afferent nerve recordings. Expression of 14 5-HT receptor subtypes, the serotonin transporter (SERT) and 5-HT producing enzymes were determined in the urothelium using RT-PCR. Retrograde labelling of bladder projecting dorsal root ganglion (DRG) neurons was used to investigate expression of 5-HT3 receptors using single cell RT-PCR, while sensory neuronal and urothelial responses to 5-HT were determined by live cell calcium imaging. 5-HT elicited bladder afferent firing predominantly via 5-HT3 receptors expressed on afferent terminals. CVH animals showed a downregulation of SERT mRNA expression in urothelium, suggesting increased 5-HT bioavailability. Granisetron, a 5-HT3 antagonist, reversed bladder afferent hypersensitivity in CVH mice. These data suggest 5-HT exerts a direct effect on bladder afferents to enhance signaling.5-HT3 antagonists could therefore be a potential therapeutic target to treat functional bladder and bowel disorders. This article is protected by copyright. All rights reserved.
Keywords: 5HT; afferent; bladder; serotonin; visceral hypersensitivity
Rights: © 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society
RMID: 1000000453
DOI: 10.1113/jp278751
Grant ID: http://purl.org/au-research/grants/nhmrc/1126378
http://purl.org/au-research/grants/nhmrc/1140297
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.