Expression of 5-HT 3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying
Abstract
Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT) 3 receptors (5-HT 3 R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT 3 R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH 2 O). Pretreatment with the 5-HT 3 R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT 3 R, visualized with an antibody directed to the COOH terminus of the rat 5-HT 3 R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT 3 R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT 3 R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.
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GLP-1 and 5-HT activate GLP-1 and 5-HT3 receptors on intestinal vagus nerve endings as key gut-brain axis signals, triggering vagal reflexes that slow gastric emptying and induce satiation.
“GLP-1 and 5-HT also activate GLP-1 and 5-HT 3 receptors on intestinal vagus nerve endings as key signals in the “gut-brain axis, ” which, in turn, triggers vagal reflexes to slow the subsequent emptying of carbohydrate from the stomach, and induce satiation (12,13).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [13]
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“GLP-1 and 5HT also activate GLP-1 and 5-HT3 receptors on intestinal vagus nerve endings as key signals in the “gut-brain axis,” which, in turn, triggers vagal reflexes to slow the subsequent emptying of carbohydrate from the stomach, and induce satiation (12, 13).”
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- Authors
- Raybould, H. E., Glatzle, J., Robin, C., Meyer, J. H., Phan, T., Wong, H., & Sternini, C.
- Affiliations
- VA Greater Los Angeles Healthcare System (US)
- Department of Anatomy, Physiology and Cell Biology, University of California Davis School of Veterinary Medicine, Davis 95616; and CURE Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, Division of Digestive Diseases, Departments of
- Medicine and
- University of California, Los Angeles (US)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2003-03-01
- Volume
- 284
- Issue
- 3
- Pages
- G367-G372
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2049378139
- Cited by
- 164
- References
- 38
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 11 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 6 · 2016: 2 · 2015: 10 · 2014: 8 · 2013: 11 · 2012: 5
- FWCI
- 10.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk035740-17)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 41301, DK-35740, DK 41004, DK57037, P30DK041301, R01DK057037)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- 5-HT3 receptor, serotonin, gastric emptying, vagal afferents, spinal afferents, intestinal perfusion, mannitol, tropisetron, enterochromaffin cells, gastric motility, visceral afferents
- MeSH terms
- Tropisetron, Animals, Duodenum, Ganglia, Spinal, Gastric Emptying, Gastrointestinal Motility, Glucose, Immunohistochemistry, Indoles, Intestines, Male, Neurons, Efferent, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Rats, Sprague-Dawley, Microscopy, Confocal, Receptors, Serotonin, 5-HT3, Receptors, Serotonin, 5-HT4, Rats
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