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Differential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociception

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dc.contributor.authorShe, Meng-Ping
dc.contributor.authorHsieh, Yu-Ting
dc.contributor.authorLin, Li-Yu
dc.contributor.authorTu, Chia-Hung
dc.contributor.authorWu, Ming-Shiang
dc.contributor.authorHsin, Ling-Wei
dc.contributor.authorYu, Linda Chia Hui
dc.date.accessioned2024-06-11T08:37:11Z
dc.date.available2024-06-11T08:37:11Z
dc.date.issued2024
dc.description.abstractObjectives. Aberrant serotonin (5-hydroxytryptamine, 5-HT) metabolism and neurite outgrowth were associated with abdominal pain in irritable bowel syndrome (IBS). We previously demonstrated that 5-HT receptor subtype 7 (5-HT7) was involved in visceral hypersensitivity of IBS-like mouse models. The aim was to compare the analgesic effects of a novel 5-HT7 antagonist to reference standards in mouse models and investigate the mechanisms of 5-HT7-dependent neuroplasticity. Methods. Two mouse models, including Giardia post-infection combined with water avoidance stress (GW) and post-resolution of trinitrobenzene sulfonic acid-induced colitis (PT) were used. Mice were orally administered CYY1005 (CYY, a novel 5-HT7 antagonist), alosetron (ALN, a 5-HT3 antagonist), and loperamide (LPM, an opioid receptor agonist) prior to measurement of visceromotor responses (VMR). Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin receptors (NTRs) were assessed. Results. Peroral CYY was more potent than ALN or LPM in reducing VMR values in GW and PT mice. Increased mucosal 5-HT7-expressing nerve fibers were associated with elevated Gap43 levels in the mouse colon. We observed higher colonic Ntrk2 and Ngfr expression in GW mice, and increased Bdnf expression in PT mice compared with control mice. Human SH-SY5Y cells stimulated with mouse colonic supernatant or exogenous serotonin exhibited longer nerve fibers, which CYY dose-dependently inhibited. Serotonin increased Ntrk1 and Ngfr expression via 5-HT7 but not 5-HT3 or 5-HT4, while Ntrk2 upregulation was dependent on all three 5-HT receptor subtypes. Conclusions. Stronger analgesic effects by peroral CYY were observed compared with reference standards in two IBS-like mouse models. The 5-HT7-dependent NTR upregulation and neurite elongation may be involved in intestinal hypernociceptiones
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dc.format.extent17es
dc.identifier.citationHistology and Histopathology Vol. 39, nº7 (2024)
dc.identifier.doihttps://doi.org/10.14670/HH-18-687
dc.identifier.doi0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/142216
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectIrritable bowel syndromees
dc.subjectNerve hypersensitivityes
dc.subjectSerotonin receptorses
dc.subjectNeurotrophin receptorses
dc.subjectNeurite outgrowthes
dc.subjectEnteric nervous systemes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleDifferential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociceptiones
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.39, nº7 (2024)