ArticleGastroenterology2007
Cyclic AMP regulates bicarbonate secretion in cholangiocytes through release of ATP into bile.
Article in Gastroenterology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71 citing papers in PubMed, 139 citations in OpenAlex.
- Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools.Physiological reviews · 2026Review
- Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation.Biomedicines · 2026Article
- Clinical management of autoimmune liver diseases: juncture, opportunities, and challenges ahead.Immunologic research · 2025Review
- New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage.World journal of gastroenterology · 2023Review
- Active enterohepatic cycling is not required for the choleretic actions of 24-norUrsodeoxycholic acid in mice.JCI insight · 2023Article
- Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products.Frontiers in immunology · 2023Review
- Systematic analysis of the expression and prognostic value of ITPR1 and correlation with tumor infiltrating immune cells in breast cancer.BMC cancer · 2022Article
- Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4).Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Roles of Non-Coding RNAs in Primary Biliary Cholangitis.Frontiers in molecular biosciences · 2022Review
- Review
- Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis.Gut · 2021Article
- Therapeutic Opportunities of GPBAR1 in Cholestatic Diseases.Frontiers in pharmacology · 2021Review
- Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Type 3 Inositol 1,4,5-Trisphosphate Receptor Is Increased and Enhances Malignant Properties in Cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2020Article
- Review
- Inositol 1,4,5-trisphosphate receptor in the liver: Expression and function.World journal of gastroenterology · 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
- Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies.International journal of molecular sciences · 2018Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsBicarbonate secretion is a primary function of cholangiocytes. Either adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca(2+) can mediate bicarbonate secretion, but these are thought to act through separate pathways. We examined the role of the inositol 1,4,5-trisphosphate receptor (InsP3R) in mediating bicarbonate secretion because this is the only intracellular Ca(2+) release channel in cholangiocytes.
methodsIntrahepatic bile duct units (IBDUs) were microdissected from rat liver then luminal pH was examined by confocal microscopy during IBDU microperfusion. Cyclic AMP was increased using forskolin or secretin, and Ca(2+) was increased using acetylcholine (ACh) or adenosine triphosphate (ATP). Apyrase was used to hydrolyze extracellular ATP, and suramin was used to block apical P2Y ATP receptors. In selected experiments, IBDUs were pretreated with short interfering RNA (siRNA) to silence expression of specific InsP3R isoforms.
resultsBoth cAMP and Ca(2+) agonists increased luminal pH. The effect of ACh on luminal pH was reduced by siRNA for basolateral (types I and II) but not apical (type III) InsP3R isoforms. The effect of forskolin on luminal pH was reduced by a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and by siRNA for the type III InsP3R. Luminal apyrase or suramin blocked the effects of forskolin but not ACh on luminal pH.
conclusionsCyclic AMP-induced ductular bicarbonate secretion depends on an autocrine signaling pathway that involves CFTR, apical release of ATP, stimulation of apical nucleotide receptors, and then activation of apical, type III InsP3Rs. The primary role of CFTR in bile duct secretion may be to regulate secretion of ATP rather than to secrete chloride and/or bicarbonate.
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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.