ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Experimental Acute Pancreatitis Models: History, Current Status, and Role in Translational Research.Frontiers in physiology · 2020Pooled it
- PARting Neuroinflammation with Protease-Activated Receptor 2 Pepducins.The Journal of pharmacology and experimental therapeutics · 2024Article
- Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.Frontiers in immunology · 2024Review
- PAR2: The Cornerstone of Pancreatic Diseases.Physiological research · 2022Review
- Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Trypsin activity governs increased susceptibility to pancreatitis in mice expressing human PRSS1R122H.The Journal of clinical investigation · 2020Article
- PAR2 controls cholesterol homeostasis and lipid metabolism in nonalcoholic fatty liver disease.Molecular metabolism · 2019Article
- Trace amine-associated receptor 1 (TAAR1) promotes anti-diabetic signaling in insulin-secreting cells.The Journal of biological chemistry · 2019Article
- PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis Models.The Journal of investigative dermatology · 2019Article
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Trypsin-protease activated receptor-2 signaling contributes to pancreatic cancer pain.Oncotarget · 2017Article
- The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications.International journal of molecular sciences · 2017Review
- Targeting Liver Fibrosis with a Cell-penetrating Protease-activated Receptor-2 (PAR2) Pepducin.The Journal of biological chemistry · 2016Article
- Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis.Molecular medicine (Cambridge, Mass.) · 2015Article
- TRPV4 as a therapeutic target for joint diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- Pepducins and Other Lipidated Peptides as Mechanistic Probes and Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Abnormal interactions between perifollicular mast cells and CD8+ T-cells may contribute to the pathogenesis of alopecia areata.PloS one · 2014Article
- Enteric bacterial proteases in inflammatory bowel disease- pathophysiology and clinical implications.World journal of gastroenterology · 2013Review
- [Novel achievements in development and application of GPCR-peptides].Zhurnal evoliutsionnoi biokhimii i fiziologiiReview
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2(-/-) mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca(2+) concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury induced by endoscopic retrograde cholangiopancreatography (ERCP). This reduction in pancreatitis severity is observed when the pepducin is given before or 2 h after bile acid infusion but not when it is given 5 h after bile acid infusion. Conversely, P2pal-18S increases the severity of secretagogue-induced pancreatitis. In vitro studies indicate that P2pal-18S protects acinar cells against bile acid-induced injury/death, but it does not alter bile acid-induced intracellular zymogen activation. These studies are the first to report the effects of an effective PAR2 pharmacological inhibitor on pancreatic acinar cells and on the severity of experimental pancreatitis. They raise the possibility that a pepducin such as P2pal-18S might prove useful in the clinical management of patients at risk for developing severe biliary pancreatitis such as occurs following ERCP.
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