Serotonin Signaling in the Gastrointestinal Tract:
By G. Mawe, J. Hoffman. Nature Reviews Gastroenterology &Hepatology, 2013
1,016 citations recorded by the source corpus.
Serotonin (5-HT) has been recognized for decades as an important signalling molecule in the gut, but it is still revealing its secrets. Novel gastrointestinal functions of 5-HT continue to be discovered, as well as distant actions of gut-derived 5-HT, and we are learning how 5-HT signalling is altered in gastrointestinal disorders. Conventional functions of 5-HT involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion and vasodilation. Activation of extrinsic vagal and spinal afferent fibres results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts nonconventional actions such as promoting inflammation and serving as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, originating in the gut, promotes haemostasis, influences bone development and serves many other functions. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhoea or constipation, respectively, and the synthetic enzyme tryptophan hydroxylase has also been targeted. Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. We provide an overview of these serotonergic actions and treatment strategies.
Subfields: Gastroenterology, Nutrition and Dietetics, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/2e4074c6ffd7848e8e86be350d993aee63b87162
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Citations in the corpus
- Gut microbes promote colonic serotonin production through an effect of short‐chain fatty acids on enterochromaffin cells (2015, background): “SEROTONIN [5-HYDROXYTRYPTAMINE (5-HT)] is a neurotransmitter andhormonewith diverse biologic functions, which include modulation of intestinal secretion and motility (1, 2).”
- Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. (2018, background): “Peripheral 5-HT triggers numerous functions in the gastrointestinal tract and is implicated in a wide range of human physiological functions by activating specific 5-HT receptors (Mawe and Hoffman, 2013).”
- Kynurenine pathway metabolism and the microbiota‐gut‐brain axis (2017, background): “Whilst serotonergic signalling is critical in CNS and ENS function, a full review is not within the scope of this article (See (Gershon and Tack, 2007; Mawe and Hoffman, 2013; O’Mahony et al., 2015; Spiller, 2008) for excellent reviews on this topic).”
- Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis (2019, background): “Enteroendocrine cell (EEC) is one subtype of epithelial cells (less than 1%), which secrete various factors in metabolic processing of dietary nutrients [120, 121].”
- Minireview: Gut microbiota: the neglected endocrine organ. (2014, background): “As well as a direct action on the gut mucosa and the enteric nervous system (ENS), the metabolic output of the gut microbiota gives it a reach well beyond the local GI compartment.”
- Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. (2019, background): “On the one hand, endogenous serotonin in the gut is mainly released from ECs in response to a number of stimuli (26).”
- Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. (2017, neutral): “…epithelia), these unique cells produce >90% of the body’s serotonin and have been suggested to affect a variety of physiological and pathophysiological states, such as gastrointestinal (GI) motility and secretion, nausea, and visceral hypersensitivity (Gershon, 2013; Mawe and Hoffman, 2013).”
- Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis (2015, neutral): “More than 90% of the body’s 5-HT is synthesized in the gut, where 5-HT activates as many as 14 different 5-HT receptor subtypes (Gershon and Tack, 2007) located on enterocytes (Hoffman et al., 2012), enteric neurons (Mawe and Hoffman, 2013), and immune cells (Baganz and Blakely, 2013).”