ArticleNeurogastroenterology and motility2016
Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons.
Article in Neurogastroenterology and motility, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- The Enteric Neuronal Circuitry: A Key Ignored Player in Nutrient Sensing Along the Gut-Brain Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- New Developments in Bile Acid Diarrhea.Gastroenterology & hepatology · 2023Article
- Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine.Neurogastroenterology and motility · 2023Article
- Intestinal secretory mechanisms and diarrhea.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Critical roles of bile acids in regulating intestinal mucosal immune responses.Therapeutic advances in gastroenterology · 2021Review
- The Role of Bile Acids in Chronic Diarrhea.The American journal of gastroenterology · 2020Review
- Bile Acid Receptors and Gastrointestinal Functions.Liver research (Beijing, China) · 2019Article
- A Novel Antiserum Against a Predicted Human Peripheral Choline Acetyltransferase (hpChAT) for Labeling Neuronal Structures in Human Colon.Frontiers in neuroanatomy · 2019Article
- Elobixibat for the treatment of constipation.Expert review of gastroenterology & hepatology · 2018Article
- Update on Bile Acid Malabsorption: Finally Ready for Prime Time?Current gastroenterology reports · 2018Review
- Bile acid signaling and bariatric surgery.Liver research (Beijing, China) · 2017Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundRecent evidence from rat neuron-free mucosa study suggests that the membrane bile acid receptor TGR5 decreases colonic secretion under basal and stimulated conditions. As submucosal neurons are key players in secretory processes and highly express TGR5, we investigated their role in TGR5 agonist-induced inhibition of secretion and the pathways recruited.
methodsTGR5 expression and localization were assessed in rat proximal (pC) and distal (dC) colon by qPCR and immunohistochemistry with double labeling for cholinergic neurons in whole-mount preparations. The influence of a selective (INT-777) or weak (ursodeoxycholic acid, UDCA) TGR5 agonist on colonic secretion was assessed in Ussing chambers, in dC preparation removing seromuscular ± submucosal tissues, in the presence of different inhibitors of secretion pathways. KEY
resultsTGR5 mRNA is expressed in full thickness dC and pC and immunoreactivity is located in colonocytes and pChAT-positive neurons. Addition of INT-777, and less potently UDCA, decreased colonic secretion in seromuscular stripped dC by -58.17± 2.6%. INT-777 effect on basal secretion was reduced in neuron-free and TTX-treated mucosal-submucosal preparations. Atropine, hexamethonium, indomethacin, and L-NAME all reduced significantly INT-777's inhibitory effect while the 5-HT CONCLUSIONS & INFERENCES: TGR5 activation inhibits basal and stimulated distal colonic secretion in rats by acting directly on epithelial cells and also inhibiting submucosal neurons. This could represent a counter-regulatory mechanism, at the submucosal level, of the known prosecretory effect of bile acids in the colon.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.