ArticleGastroenterology2007
Ursodeoxycholic acid stimulates cholangiocyte fluid secretion in mice via CFTR-dependent ATP secretion.
Article in Gastroenterology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 114 citations in OpenAlex.
- Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools.Physiological reviews · 2026Review
- Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice.Journal of hepatology · 2024Article
- Active enterohepatic cycling is not required for the choleretic actions of 24-norUrsodeoxycholic acid in mice.JCI insight · 2023Article
- Pathophysiological mechanisms of liver injury in COVID-19.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Mechanosensor transient receptor potential vanilloid member 4 (TRPV4) regulates mouse cholangiocyte secretion and bile formation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Pediatric Cholestatic Liver Disease: Review of Bile Acid Metabolism and Discussion of Current and Emerging Therapies.Frontiers in medicine · 2020Review
- Review
- Animal models for cystic fibrosis liver disease (CFLD).Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Effects of Endotoxin on Type 3 Inositol 1,4,5-Trisphosphate Receptor in Human Cholangiocytes.Hepatology (Baltimore, Md.) · 2019Article
- Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota.Cellular and molecular gastroenterology and hepatology · 2019Review
- Calcium Signaling in Cholangiocytes: Methods, Mechanisms, and Effects.International journal of molecular sciences · 2018Review
- Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A ClHepatology (Baltimore, Md.) · 2018Article
- Animal models of biliary injury and altered bile acid metabolism.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- Src kinase inhibition reduces inflammatory and cytoskeletal changes in ΔF508 human cholangiocytes and improves cystic fibrosis transmembrane conductance regulator correctors efficacy.Hepatology (Baltimore, Md.) · 2018Article
- Calcium Signaling in Liver Injury and Regeneration.Frontiers in medicine · 2018Review
- The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity.Hepatology (Baltimore, Md.) · 2016Article
- Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations.Molecular neurobiology · 2016Article
- Regulation of mechanosensitive biliary epithelial transport by the epithelial Na(+) channel.Hepatology (Baltimore, Md.) · 2016Article
- Stimulation of nuclear receptor peroxisome proliferator-activated receptor-γ limits NF-κB-dependent inflammation in mouse cystic fibrosis biliary epithelium.Hepatology (Baltimore, Md.) · 2015Article
- Calcium signaling and secretion in cholangiocytes.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2015Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsCholangiopathies are characterized by impaired cholangiocyte secretion. Ursodeoxycholic acid (UDCA) is widely used for cholangiopathy treatment, but its effects on cholangiocyte secretory functions remain unclear and are the subject of this study.
methodsPolarized mouse cholangiocytes in tubular (isolated bile-duct units [IBDU]) or monolayer configuration were obtained from wild-type (WT) and B6-129-Cftr(tm1Kth) and Cftr(tm1Unc) mice that are defective in CFTR, an adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated Cl(-) channel expressed in cholangiocytes. Fluid secretion was assessed by video-optical planimetry, Cl(-) and Ca(2+) efflux by microfluorimetry (6-methoxy-N-ethylquinolinium chloride, fura-2, and fluo-4), adenosine triphosphate (ATP) secretion by luciferin-luciferase assay, and protein kinase C (PKC) by Western blot.
resultsUDCA stimulated fluid secretion and Cl(-) efflux in WT-IBDU but not in CFTR-KO-IBDU or in WT-IBDU exposed to CFTR inhibitors. UDCA did not affect intracellular cAMP levels but increased [Ca(2+)]i in WT and not in CFTR-KO cholangiocytes. UDCA stimulated apical ATP secretion in WT but not in CFTR-KO cholangiocytes. UDCA-stimulated [Ca(2+)]i increase was inhibited by suramin, a purinergic 2Y-receptor inhibitor. UDCA stimulated the translocation of PKC-alpha and PKC-epsilon to the plasma membrane. UDCA-stimulated secretion was inhibited by 2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid and by phospholipase C and PKC inhibitors. UDCA increased ATP output in isolated perfused livers from WT but not from CFTR-KO mice.
conclusionsOur data indicate that UDCA stimulates a CFTR-dependent apical ATP release in cholangiocytes. Secreted ATP activates purinergic 2Y receptors, and, through [Ca(2+)]i increase and PKC activation stimulates Cl(-) efflux and fluid secretion. These data support the concept that CFTR plays a role in modulating purinergic signaling in secretory epithelia and suggest a novel mechanism explaining the choleretic effect of UDCA.
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Registered trials
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.