ArticleAmerican journal of physiology. Cell physiology2013
Chenodeoxycholic acid stimulates Cl(-) secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Gut microbiota and constipation: from causal evidence to therapeutic strategies-a state-of-the-art narrative review.Frontiers in microbiology · 2026Review
- Zinc inhibits cAMP-induced ClAmerican journal of physiology. Cell physiology · 2025Article
- Bile Acid Diarrhea Is Associated With an Increased Risk of Type 2 Diabetes and Cardiovascular Disease: A Nationwide Cohort Study.Clinical and translational gastroenterology · 2025Article
- Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant.Microbiome · 2024Article
- Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells.The Journal of clinical investigation · 2024Article
- Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas.Translational research : the journal of laboratory and clinical medicine · 2024Article
- Article
- SLC26A3 (DRA) is stimulated in a synergistic, intracellular CaAmerican journal of physiology. Cell physiology · 2023Article
- Multi-strain probiotics alleviate loperamide-induced constipation by adjusting the microbiome, serotonin, and short-chain fatty acids in rats.Frontiers in microbiology · 2023Article
- Crosstalk between the Gut Microbiome and Colonic Motility in Chronic Constipation: Potential Mechanisms and Microbiota Modulation.Nutrients · 2022Review
- The Effect of Lithocholic Acid on the Gut-Liver Axis.Frontiers in pharmacology · 2022Review
- The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation.Frontiers in nutrition · 2021Review
- Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome.World journal of gastroenterology · 2020Article
- Altered absorptive function in the gall bladder during cholesterol gallstone formation is associated with abnormal NHE3 complex formation.Journal of physiology and biochemistry · 2020Article
- The Structure and Function of the Human Small Intestinal Microbiota: Current Understanding and Future Directions.Cellular and molecular gastroenterology and hepatology · 2020Review
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Analysis of Fecal Primary Bile Acids Detects Increased Stool Weight and Colonic Transit in Patients With Chronic Functional Diarrhea.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2019Article
- Bile Acid Receptors and Gastrointestinal Functions.Liver research (Beijing, China) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
High levels of chenodeoxycholic acid (CDCA) and deoxycholic acid stimulate Cl(-) secretion in mammalian colonic epithelia. While different second messengers have been implicated in this action, the specific signaling pathway has not been fully delineated. Using human colon carcinoma T84 cells, we elucidated this cascade assessing Cl(-) transport by measuring I(-) efflux and short-circuit current (Isc). CDCA (500 μM) rapidly increases I(-) efflux, and we confirmed by Isc that it elicits a larger response when added to the basolateral vs. apical surface. However, preincubation with cytokines increases the monolayer responsiveness to apical addition by 55%. Nystatin permeabilization studies demonstrate that CDCA stimulates an eletrogenic apical Cl(-) but not a basolateral K(+) current. Furthermore, CDCA-induced Isc was inhibited (≥67%) by bumetanide, BaCl2, and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. CDCA-stimulated Isc was decreased 43% by the adenylate cyclase inhibitor MDL12330A and CDCA increases intracellular cAMP concentration. The protein kinase A inhibitor H89 and the microtubule disrupting agent nocodazole, respectively, cause 94 and 47% reductions in CDCA-stimulated Isc. Immunoprecipitation with CFTR antibodies, followed by sequential immunoblotting with Pan-phospho and CFTR antibodies, shows that CDCA increases CFTR phosphorylation by approximately twofold. The rapidity and side specificity of the response to CDCA imply a membrane-mediated process. While CDCA effects are not blocked by the muscarinic receptor antagonist atropine, T84 cells possess transcript and protein for the bile acid G protein-coupled receptor TGR5. These results demonstrate for the first time that CDCA activates CFTR via a cAMP-PKA pathway involving microtubules and imply that this occurs via a basolateral membrane receptor.
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