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Altered 5-Hydroxytryptamine Signaling in Patients With Constipation- and Diarrhea-Predominant Irritable Bowel Syndrome
Open accessAbstract
Background & aims Evidence suggests that postprandial platelet-depleted plasma 5-hydroxytryptamine (5-HT) concentrations may be abnormal in irritable bowel syndrome (IBS). However, interpretation of the data has been hampered by the variable methodology and rather small numbers used in previous studies. Therefore, the aim of this study was to measure concentrations of platelet-depleted plasma 5-HT and its metabolite 5-HIAA under fasting and fed conditions in a large group of patients with diarrhea-predominant (d-) and constipation-predominant (c-) IBS, compared with controls. The ratio of plasma 5-HIAA:5-HT and platelet stores was also assessed.Methods Twenty-nine c-IBS patients (aged, 19-53 years), 55 d-IBS patients (aged, 19-52 years), and 35 healthy volunteers (aged, 18-46 years) had platelet-depleted plasma 5-HT/5-HIAA concentrations measured using reverse-phase, high-performance liquid chromatography with fluorimetric detection before and after a standard meal.Results d-IBS patients had raised platelet-depleted plasma 5-HT concentrations under fasting and fed conditions (P < .05). However, the postprandial relative to fasting concentration was similar to controls. In contrast, c-IBS patients failed to show an increase in platelet-depleted plasma 5-HT concentration with meal ingestion compared with controls (P < .01). c-IBS was associated with decreased 5-HIAA (P < .01) but normal 5-HIAA:5-HT ratio and d-IBS with normal 5-HIAA concentrations but reduced 5-HIAA:5-HT ratio (P < .005). C-IBS but not d-IBS patients had increased platelet 5-HT.Conclusions These results support the concept that d-IBS is characterized by reduced 5-HT reuptake, whereas impaired release may be a feature of c-IBS. These results also provide a rational basis for current pharmacologic approaches involving modulation of different 5-HT receptors in c- and d-IBS.
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“Changes in gastrointestinal motility may be influenced by alterations in serotonin (5-Hydroxytryptamine (5-HT)) metabolism, 49 with high levels reported in patients with IBS-D, and low levels in IBS-C.50”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [50]
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Metadata
- Authors
- Atkinson, W., Lockhart, S., Whorwell, P. J., Keevil, B., & Houghton, L. A.
- Corresponding author
- Houghton, Lesley A.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 130
- Issue
- 1
- Pages
- 34-43
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2128077096
- Cited by
- 355
- References
- 41
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 15 · 2023: 21 · 2022: 20 · 2021: 30 · 2020: 18 · 2019: 12 · 2018: 11 · 2017: 15 · 2016: 15 · 2015: 12 · 2014: 30 · 2013: 16 · 2012: 20
- FWCI
- 18.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- irritable bowel syndrome, irritable bowel syndrome with constipation, diarrhea-predominant irritable bowel syndrome, serotonin, 5-hydroxyindoleacetic acid, serotonin uptake, serotonin release, serotonin receptors
- MeSH terms
- Adult, Chromatography, High Pressure Liquid, Constipation, Diarrhea, Fasting, Female, Humans, Hydroxyindoleacetic Acid, Male, Middle Aged, Serotonin, Signal Transduction, Case-Control Studies, Postprandial Period, Irritable Bowel Syndrome
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