Konthapakdee, N., Grundy, L., O'Donnell, T. et al. (4 more authors) (2019) Serotonin exerts a direct modulatory role on bladder afferent firing in mice. The Journal of Physiology, 597 (21). pp. 5247-5264. ISSN 0022-3751
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Physiological Society. This is an author-produced version of a paper subsequently published in The Journal of Physiology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | afferent; bladder; serotonin; 5HT; visceral hypersensitivity |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number European Commission - FP6/FP7 TRUST - 238541 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Sep 2019 10:59 |
Last Modified: | 16 Dec 2021 10:04 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1113/jp278751 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151211 |