ArticleThe Journal of clinical investigation1999
Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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.
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
56 citing papers in PubMed, 182 citations in OpenAlex.
- Purified human pancreatic duct cell culture conditions defined by serum-free high-content growth factor screening.PloS one · 2012Trial
- Pathologically relevant trypsinogen activation in pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- PAR2: The Cornerstone of Pancreatic Diseases.Physiological research · 2022Review
- Measurement of novel intestinal secretory and barrier pathways and effects of proteases.Neurogastroenterology and motility · 2019Review
- Use of Nasopancreatic Drainage for Severe Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Case Series.Internal medicine (Tokyo, Japan) · 2018Article
- Contributions of protein kinases and β-arrestin to termination of protease-activated receptor 2 signaling.The Journal of general physiology · 2016Article
- Proteinase activated-receptors-associated signaling in the control of gastric cancer.World journal of gastroenterology · 2014Review
- Epithelial monolayer culture system for real-time single-cell analyses.Physiological reports · 2014Article
- Article
- Effects of protease-activated receptors (PARs) on intracellular calcium dynamics of acinar cells in rat lacrimal glands.Histochemistry and cell biology · 2013Article
- Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- Physiology and pathophysiology of bicarbonate secretion by pancreatic duct epithelium.Nagoya journal of medical science · 2012Review
- Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion.Physiological reviews · 2012Review
- Protease-activated receptor 2 signaling in inflammation.Seminars in immunopathology · 2012Review
- Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl⁻ channels and luminal anion exchangers.Gastroenterology · 2011Article
- Lymphocyte function antigen-1 regulates neutrophil recruitment and tissue damage in acute pancreatitis.British journal of pharmacology · 2011Article
- Review
- Article
- Transcriptional regulation of CXC-ELR chemokines KC and MIP-2 in mouse pancreatic acini.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds and activates the receptor. We examined the secretory effects of trypsin, mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2, corresponding to the PAR-2 tethered ligand) stimulated both an 125I- efflux inhibited by Ca2+-activated Cl- channel inhibitors and a 86Rb+ efflux inhibited by a Ca2+-activated K+ channel inhibitor. The reverse peptide (LRGILS-NH2) and inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short-circuit current from the basolateral, but not apical, surface of PDEC monolayers. In monolayers permeabilized basolaterally or apically with nystatin, AP activated apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+]i in PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2 expression on dog pancreatic ducts and PDEC was verified by immunofluorescence. Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+]i and activate ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated, PAR-2-mediated ductal secretion may promote clearance of toxins and debris.
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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.