ArticleHepatology (Baltimore, Md.)2010
Adenosine triphosphate release and purinergic (P2) receptor-mediated secretion in small and large mouse cholangiocytes.
Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Isolation and long-term culture of primary mouse cholangiocytes that retain biophysical properties and distinct Cl-conductances: An initial study.Physiological reports · 2026Article
- Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease.Molecular therapy. Nucleic acids · 2025Review
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- Targeting P2X Receptors-Current Progress in Sepsis.International journal of inflammation · 2025Review
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- P2Y2 purinergic receptor gene deletion protects mice from bacterial endotoxin and sepsis-associated liver injury and mortality.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Piezo1-Pannexin1 complex couples force detection to ATP secretion in cholangiocytes.The Journal of general physiology · 2021Article
- The bile acid-sensitive ion channel (BASIC) mediates bile acid-dependent currents in bile duct epithelial cells.Pflugers Archiv : European journal of physiology · 2021Article
- Pathophysiological Role of Purinergic P2X Receptors in Digestive System Diseases.Frontiers in physiology · 2021Review
- Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury.Hepatology (Baltimore, Md.) · 2020Review
- Mechanosensor transient receptor potential vanilloid member 4 (TRPV4) regulates mouse cholangiocyte secretion and bile formation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A ClHepatology (Baltimore, Md.) · 2018Article
- H19 promotes cholestatic liver fibrosis by preventing ZEB1-mediated inhibition of epithelial cell adhesion molecule.Hepatology (Baltimore, Md.) · 2017Article
- Cell culture: complications due to mechanical release of ATP and activation of purinoceptors.Cell and tissue research · 2017Review
- Regulation of mechanosensitive biliary epithelial transport by the epithelial Na(+) channel.Hepatology (Baltimore, Md.) · 2016Article
- PKCα regulates TMEM16A-mediated Cl⁻ secretion in human biliary cells.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Functional and structural features of cholangiocytes in health and disease.Cellular and molecular gastroenterology and hepatology · 2015Article
- Nuclear Factor, Erythroid 2-Like 2 Regulates Expression of Type 3 Inositol 1,4,5-Trisphosphate Receptor and Calcium Signaling in Cholangiocytes.Gastroenterology · 2015Article
- P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Origin of myofibroblasts in the fibrotic liver in mice.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledAdenosine triphosphate (ATP) is released from cholangiocytes into bile and is a potent secretogogue by increasing intracellular Ca²(+) and stimulating fluid and electrolyte secretion via binding purinergic (P2) receptors on the apical membrane. Although morphological differences exist between small and large cholangiocytes (lining small and large bile ducts, respectively), the role of P2 signaling has not been previously evaluated along the intrahepatic biliary epithelium. The aim of these studies therefore was to characterize ATP release and P2-signaling pathways in small (MSC) and large (MLC) mouse cholangiocytes. The findings reveal that both MSCs and MLCs express P2 receptors, including P2X4 and P2Y2. Exposure to extracellular nucleotides (ATP, uridine triphosphate, or 2',3'-O-[4-benzoyl-benzoyl]-ATP) caused a rapid increase in intracellular Ca²(+) concentration and in transepithelial secretion (I(sc)) in both cell types, which was inhibited by the Cl(-) channel blockers 5-nitro-2-(-3-phenylpropylamino)-benzoic acid (NPPB) or niflumic acid. In response to mechanical stimulation (flow/shear or cell swelling secondary to hypotonic exposure), both MSCs and MLCs exhibited a significant increase in the rate of exocytosis, which was paralleled by an increase in ATP release. Mechanosensitive ATP release was two-fold greater in MSCs compared to MLCs. ATP release was significantly inhibited by disruption of vesicular trafficking by monensin in both cell types.
conclusionThese findings suggest the existence of a P2 signaling axis along intrahepatic biliary ducts with the "upstream" MSCs releasing ATP, which can serve as a paracrine signaling molecule to "downstream" MLCs stimulating Ca²(+)-dependent secretion. Additionally, in MSCs, which do not express the cystic fibrosis transmembrane conductance regulator, Ca²(+)-activated Cl(-) efflux in response to extracellular nucleotides represents the first secretory pathway clearly identified in these cholangiocytes derived from the small intrahepatic ducts.
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Registered trials
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