ArticleGastroenterology2011
Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl⁻ channels and luminal anion exchangers.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Restoration of energy level in the early phase of acute pediatric pancreatitis.World journal of gastroenterology · 2017Pooled it
- CFTR IVS8 Poly-T Variation Affects Severity of Acute Pancreatitis in Women.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2019Trial
- Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study.The Lancet. Respiratory medicine · 2016Trial
- Intraductal digestive enzyme accumulation drives lethal hemorrhagic necrotizing pancreatitis and enables therapeutic intervention.Research square · 2026Article
- Pathologically relevant trypsinogen activation in pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Cystic Fibrosis of the Pancreas: In Vitro Duct Models for CFTR-Targeted Translational Research.International journal of molecular sciences · 2026Review
- Deletion of the WD40 domain of ATG16L1 exacerbates acute pancreatitis, abolishes LAP-like non-canonical autophagy and slows trypsin degradation.Autophagy · 2025Article
- Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis.Clinical and translational medicine · 2024Article
- Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium.Cellular & molecular biology letters · 2024Article
- MSCs Deliver Hypoxia-Treated Mitochondria Reprogramming Acinar Metabolism to Alleviate Severe Acute Pancreatitis Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Human pancreatic ductal organoids with controlled polarity provide a novel ex vivo tool to study epithelial cell physiology.Cellular and molecular life sciences : CMLS · 2023Article
- The role of CaCell calcium · 2023Review
- Precision Medicine in Pancreatitis: The Future of Acute Pancreatitis Care.Function (Oxford, England) · 2023Review
- PAR2: The Cornerstone of Pancreatic Diseases.Physiological research · 2022Review
- Autophagy, Acute Pancreatitis and the Metamorphoses of a Trypsinogen-Activating Organelle.Cells · 2022Review
- Review
- Pancreatitis severity in mice with impaired CFTR function but pancreatic sufficiency is mediated via ductal and inflammatory cells-Not acinar cells.Journal of cellular and molecular medicine · 2021Article
- Review
- LAP-like non-canonical autophagy and evolution of endocytic vacuoles in pancreatic acinar cells.Autophagy · 2020Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsThe effects of trypsin on pancreatic ductal epithelial cells (PDECs) vary among species and depend on the localization of proteinase-activated receptor 2 (PAR-2). We compared PAR-2 localization in human and guinea-pig PDECs, and used isolated guinea pig ducts to study the effects of trypsin and a PAR-2 agonist on bicarbonate secretion.
methodsPAR-2 localization was analyzed by immunohistochemistry in guinea pig and human pancreatic tissue samples (from 15 patients with chronic pancreatitis and 15 without pancreatic disease). Functionally, guinea pig PDECs were studied by microperfusion of isolated ducts, measurements of intracellular pH and intracellular Ca(2+) concentration, and patch clamp analysis. The effect of pH on trypsinogen autoactivation was assessed using recombinant human cationic trypsinogen.
resultsPAR-2 localized to the apical membrane of human and guinea pig PDECs. Trypsin increased intracellular Ca(2+) concentration and intracellular pH and inhibited secretion of bicarbonate by the luminal anion exchanger and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Autoactivation of human cationic trypsinogen accelerated when the pH was reduced from 8.5 to 6.0. PAR-2 expression was strongly down-regulated, at transcriptional and protein levels, in the ducts of patients with chronic pancreatitis, consistent with increased activity of intraductal trypsin. Importantly, in PAR-2 knockout mice, the effects of trypsin were markedly reduced.
conclusionsTrypsin reduces pancreatic ductal bicarbonate secretion via PAR-2-dependent inhibition of the apical anion exchanger and the CFTR Cl(-) channel. This could contribute to the development of chronic pancreatitis by decreasing luminal pH and promoting premature activation of trypsinogen in the pancreatic ducts.
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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.