ArticleGastroenterology2012
Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 264 citations in OpenAlex.
- Prokinetic drugs that stimulate 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Review of nutrition management of pediatric intestinal pseudo-obstruction.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2026Review
- Dup15q model mice exhibit impaired gastrointestinal motility and a constipation-like phenotype, alleviated by prucalopride.Translational psychiatry · 2026Article
- Gut Microbiota-Mediated Modulation of Intestinal Serotonin by Tea Polyphenols: Potential Mechanisms and Implications for Metabolic Health.Nutrients · 2026Review
- Saffron Alters Microbial Amino Acid Metabolism and Neurotransmitter Production in a Defined Gut Consortium.Food science & nutrition · 2026Article
- Effects of Three Microbiome-Based Therapies on Loperamide-Induced Constipation in Mice by Restoring Intestinal Motility and Modulating the Intestinal Microbiota.Probiotics and antimicrobial proteins · 2026Article
- Potential and Future Therapeutic Applications of Eicosapentaenoic/Docosahexaenoic Acid and Probiotics in Chronic Low-Grade Inflammation.Biomedicines · 2025Review
- Interactions between CNS regulation and serotonergic modulation of crayfish hindgut motility.Royal Society open science · 2025Article
- Flavanones as Modulators of Gut Microbiota and Cognitive Function.Molecules (Basel, Switzerland) · 2025Review
- Serotonin signaling to regulate energy metabolism: a gut microbiota perspective.Life metabolism · 2025Review
- Bacteria Engineered to Produce Serotonin Modulate Host Intestinal Physiology.ACS synthetic biology · 2024Article
- Systematic Insights into the Relationship between the Microbiota-Gut-Brain Axis and Stroke with the Focus on Tryptophan Metabolism.Metabolites · 2024Review
- The Human Microbiome-A Physiologic Perspective.Comprehensive Physiology · 2024Review
- Managing gastrointestinal manifestations in systemic sclerosis, a mechanistic approach.Expert review of clinical immunology · 2024Review
- Amperometry approach curve profiling to understand the regulatory mechanisms governing the concentration of intestinal extracellular serotonin.Scientific reports · 2024Article
- Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's Disease Pathogenesis.Aging and disease · 2024Review
- Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.World journal of gastroenterology · 2024Review
- The 5HT4R agonist velusetrag efficacy on neuropathic chronic intestinal pseudo-obstruction in PrP-SCA7-92Q transgenic mice.Frontiers in pharmacology · 2024Article
- Activation of the 5-hydroxytryptamine 4 receptor ameliorates tight junction barrier dysfunction in the colon of type 1 diabetic mice.Acta biochimica et biophysica Sinica · 2023Article
- Protective actions of a luminally acting 5-HTNeurogastroenterology and motility · 2023Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aims5-hydroxytryptamine receptor (5-HT(4)R) agonists promote gastrointestinal motility and attenuate visceral pain, but concerns about adverse reactions have restricted their availability. We tested the hypotheses that 5-HT(4) receptors are expressed in the colonic epithelium and that 5-HT(4)R agonists can act intraluminally to increase motility and reduce visceral hypersensitivity.
methodsMucosal expression of the 5-HT(4)R was evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemical analysis of tissues from 5-HT(4)R(BAC)-enhanced green fluorescent protein mice. Amperometry, histology, and short-circuit current measurements were used to study 5-HT, mucus, and Cl(-) secretion, respectively. Propulsive motility was measured in guinea pig distal colon, and visceromotor responses were recorded in a rat model of colonic hypersensitivity. 5-HT(4)R compounds included cisapride, tegaserod, naronapride, SB204070, and GR113808.
resultsMucosal 5-HT(4) receptors were present in the small and large intestines. In the distal colon, 5-HT(4) receptors were expressed by most epithelial cells, including enterochromaffin and goblet cells. Stimulation of 5-HT(4)Rs evoked mucosal 5-HT release, goblet cell degranulation, and Cl(-) secretion. Luminal administration of 5-HT(4)R agonists accelerated propulsive motility; a 5-HT(4)R antagonist blocked this effect. Bath application of 5-HT(4)R agonists did not affect motility. Oral or intracolonic administration of 5-HT(4)R agonists attenuated visceral hypersensitivity. Intracolonic administration was more potent than oral administration, and was inhibited by a 5-HT(4)R antagonist.
conclusionsMucosal 5-HT(4) receptor activation can mediate the prokinetic and antinociceptive actions of 5-HT(4)R agonists. Colon-targeted, intraluminal delivery of 5-HT(4)R agonists might be used to promote motility and alleviate visceral pain, while restricting systemic bioavailability and resulting adverse side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.