Serotonin exerts a direct modulatory role on bladder afferent firing in mice.

Tytuł:: Serotonin exerts a direct modulatory role on bladder afferent firing in mice.
Autorzy:: Konthapakdee N; Department of Physiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand.
Grundy L; Visceral Pain Research Group, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, 5042, Australia.; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia, 5000, Australia.; Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5000, Australia.
O'Donnell T; Visceral Pain Research Group, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, 5042, Australia.; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia, 5000, Australia.; Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5000, Australia.
Garcia-Caraballo S; Visceral Pain Research Group, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, 5042, Australia.; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia, 5000, Australia.; Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5000, Australia.
Brierley SM; Visceral Pain Research Group, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, 5042, Australia.; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia, 5000, Australia.; Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5000, Australia.
Grundy D; Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Daly DM; University of Central Lancashire, Preston, UK.
Źródło:: The Journal of physiology [J Physiol] 2019 Nov; Vol. 597 (21), pp. 5247-5264. Date of Electronic Publication: 2019 Oct 13.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Oxford : Blackwell : Cambridge Univ. Press
Original Publication: London, Cambridge Univ. Press.
MeSH Terms:: Afferent Pathways/*metabolism
Neurons, Afferent/*metabolism
Serotonin/*metabolism
Urinary Bladder/*metabolism
Afferent Pathways/drug effects ; Animals ; Colon/drug effects ; Colon/metabolism ; Disease Models, Animal ; Female ; Ganglia, Spinal/drug effects ; Ganglia, Spinal/metabolism ; Granisetron/pharmacology ; Irritable Bowel Syndrome/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/metabolism ; Neurons, Afferent/drug effects ; Peripheral Nervous System/drug effects ; Peripheral Nervous System/metabolism ; Receptors, Serotonin, 5-HT3/metabolism ; Serotonin Antagonists/pharmacology ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Trinitrobenzenesulfonic Acid/pharmacology ; Urinary Bladder/drug effects
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Contributed Indexing:: Keywords: 5-HT; afferent; bladder; serotonin; visceral hypersensitivity
Substance Nomenclature:: 0 (Receptors, Serotonin, 5-HT3)
0 (Serotonin Antagonists)
0 (Serotonin Plasma Membrane Transport Proteins)
333DO1RDJY (Serotonin)
8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid)
WZG3J2MCOL (Granisetron)
Entry Date(s):: Date Created: 20190915 Date Completed: 20200908 Latest Revision: 20200908
Update Code:: 20240105
DOI:: 10.1113/JP278751
PMID:: 31520534
: Czasopismo naukowe

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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-HT 3 receptor mRNA transcripts are expressed in mouse urothelium and exert functional responses to 5-HT. Whilst 5-HT 3 receptors were not detected in mouse urothelium, 5-HT 3 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. These data suggest that the role 5-HT 3 receptors play in bladder afferent signalling warrants further study as a potential therapeutic target for functional bladder disorders.
Abstract: Serotonin (5-HT) is an excitatory mediator that in the gastrointestinal (GI) tract plays a physiological role in gut-brain 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-sensitization of shared innervation pathways between the bladder and colon. However, a direct modulatory role of 5-HT in bladder afferent signalling 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 signalling in normal mice and mice with chronic visceral hypersensitivity (CVH) following trinitrobenzenesulfonic acid-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 was determined in the urothelium using RT-PCR. Retrograde labelling of bladder-projecting dorsal root ganglion neurons was used to investigate expression of 5-HT 3 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-HT 3 receptors expressed on afferent terminals. CVH animals showed a downregulation of SERT mRNA expression in urothelium, suggesting increased 5-HT bioavailability. Granisetron, a 5-HT 3 antagonist, reversed bladder afferent hypersensitivity in CVH mice. These data suggest 5-HT exerts a direct effect on bladder afferents to enhance signalling. 5-HT 3 antagonists could therefore be a potential therapeutic target to treat functional bladder and bowel disorders.
(© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Comment in: J Physiol. 2020 Jan;598(1):23-24. (PMID: 31715639)

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