Non-conventional features of peripheral serotonin signalling — the gut and beyond
Open accessAbstract
Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.
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In mammals, 5-HT modulates host behavior, GI motility, bone remodeling, and erythrocyte health.
“In mammals, 5-HT plays diverse roles ranging from modulation of host behavior to impacting GI motility as well as influencing bone remodeling and erythrocyte health (Spohn and Mawe, 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Spohn and Mawe, 2017
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- Authors
- Spohn, S. N., & Mawe, G. M.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Mawe, Gary M.
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2017-05-10
- Volume
- 14
- Issue
- 7
- Pages
- 412-420
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC5672796
- OpenAlex
- W2612522158
- Cited by
- 282
- References
- 90
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 57 · 2023: 28 · 2022: 32 · 2021: 37 · 2020: 28 · 2019: 25 · 2018: 24 · 2017: 5
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK062267)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- serotonin, gut microbiota, enterochromaffin cells, serotonin receptors, 5-HT7 receptor, 5-HT4 receptor, gastrointestinal inflammation, colitis, hematopoiesis, metabolic homeostasis, bone remodeling, enteric reflexes, gut-brain axis
- MeSH terms
- Gastrointestinal Microbiome, Colitis, Hematopoiesis, Homeostasis, Humans, Serotonin, Signal Transduction, Bone Remodeling, Enteric Nervous System, Inflammation Mediators, Gastrointestinal Tract
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