The relationship between the effects of short‐chain fatty acids on intestinal motility in vitro and GPR43 receptor activation
Abstract
Abstract The G protein‐coupled receptors, GPR41 and GPR43, are activated by short‐chain fatty acids (SCFAs), with distinct rank order potencies. This study investigated the possibility that SCFAs modulate intestinal motility via these receptors. Luminal SCFA concentrations within the rat intestine were greatest in the caecum (c. 115 mmol L−1) and proximal colon. Using similar concentrations (0.1–100 mmol L−1), SCFAs were found to inhibit electrically evoked, neuronally mediated contractions of rat distal colon, possibly via a prejunctional site of action; this activity was independent of the presence or absence of the mucosa. By contrast, SCFAs reduced the amplitude but also reduced the threshold and increased the frequency of peristaltic contractions in guinea‐pig terminal ileum. In each model, the rank‐order of activity was acetate (C2) ≈ propionate (C3) ≈ butyrate (C4) > pentanoate (C5) ∼ formate (C1), consistent with activity at the GPR43 receptor. GPR43 mRNA was expressed throughout the rat gut, with highest levels in the colon. However, the ability of SCFAs to inhibit neuronally mediated contractions of the colon was similar in tissues from wild‐type and GPR43 gene knockout mice, with identical rank‐orders of potency. In conclusion, SCFAs can modulate intestinal motility, but these effects can be independent of the GPR43 receptor.
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Metabolic products of intestinal bacteria, such as short-chain fatty acids or chemotactic peptides, are able to stimulate the enteric nervous system and influence the rate of gut transit.
“Metabolic products of intestinal bacteria, such as short-chain fatty acids or chemotactic peptides (for example, N-formylmethionyl–leucine–phenylalanine) are able to stimulate the enteric nervous system and influence the rate of gut transit.38-40”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [39]
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- Authors
- Dass, N. B., John, A. K., Bassil, A. K., Crumbley, C. W., Shehee, W. R., Maurio, F. P., Moore, G. B. T., Taylor, C. M., & Sanger, G. J.
- Affiliations
- GlaxoSmithKline (United Kingdom) (GB)
- Princess Alexandra Hospital NHS Trust (GB)
- GlaxoSmithKline (United States) (US)
- Corresponding author
- Sanger, G. J.
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2006-12-07
- Volume
- 19
- Issue
- 1
- Pages
- 66-74
- ISSN
- 1350-1925 (ISSN-L)
- 1365-2982
- OpenAlex
- W1972978634
- Cited by
- 166
- References
- 1
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 10 · 2023: 10 · 2022: 11 · 2021: 16 · 2020: 11 · 2019: 9 · 2018: 8 · 2017: 13 · 2016: 8 · 2015: 3 · 2014: 10 · 2013: 11 · 2012: 7
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- short-chain fatty acids, GPR43, GPR41, intestinal motility, colonic smooth muscle contraction, peristalsis, prejunctional inhibition, acetate, propionate, butyrate, formate, cecum, ileum
- MeSH terms
- Animals, Carboxylic Acids, Central Nervous System, Electric Stimulation, Fatty Acids, Gastrointestinal Motility, Guinea Pigs, Ileum, Male, Peristalsis, RNA, Messenger, Rats, Sprague-Dawley, Mice, Knockout, Receptors, G-Protein-Coupled, Mice, Rats, In Vitro Techniques
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