ArticleProceedings of the National Academy of Sciences of the United States of America2013
Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 188 citations in OpenAlex.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- BCL2 inhibition in acute and chronic pancreatitis - is there a therapeutic perspective?Cell death discovery · 2026Review
- Mitochondrial dysfunction as a bridge to pathology in acute pancreatitis: From molecular insights to novel therapeutic strategies.World journal of gastroenterology · 2025Review
- TRPV6 channel function is involved in endometrial epithelial cell CaCellular and molecular life sciences : CMLS · 2025Article
- Repurposing BCL2 inhibitors: Venetoclax protects against acinar cell necrosis in acute pancreatitis by promoting apoptosis.Cell death & disease · 2025Article
- Lysine acetylation and its role in the pathophysiology of acute pancreatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Ca2+ tunneling architecture and function are important for secretion.The Journal of cell biology · 2025Article
- Combination of the CRAC Channel Inhibitor CM4620 and Galactose as a Potential Therapy for Acute Pancreatitis.Function (Oxford, England) · 2024Article
- Identifying novel acute pancreatitis sub-phenotypes using total serum calcium trajectories.BMC gastroenterology · 2024Article
- Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway.International journal of molecular sciences · 2024Article
- Research trends on traditional Chinese medicine and acute pancreatitis: A bibliometric analysis from 2007 to mid-2023.Heliyon · 2024Article
- Exploring the interplay of gut microbiota, inflammation, and LDL-cholesterol: a multiomics Mendelian randomization analysis of their causal relationship in acute pancreatitis and non-alcoholic fatty liver disease.Journal of translational medicine · 2024Article
- Ion channels in acinar cells in acute pancreatitis: crosstalk of calcium, iron, and copper signals.Frontiers in immunology · 2024Review
- Neutrophil-specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-associated Acute Lung Injury.Function (Oxford, England) · 2024Article
- Article
- The role of CaCell calcium · 2023Review
- Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Relationship between Cholesterol-Related Lipids and Severe Acute Pancreatitis: From Bench to Bedside.Journal of clinical medicine · 2023Review
- Watching Living Cells in Action in the Exocrine Pancreas: The Palade Prize Lecture.Function (Oxford, England) · 2023Review
- Endogenous Amyloid-formed CaFunction (Oxford, England) · 2023Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca(2+) concentration inside pancreatic acinar cells ([Ca(2+)]i), due to excessive release of Ca(2+) stored inside the cells followed by Ca(2+) entry from the interstitial fluid. The sustained [Ca(2+)]i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca(2+) release-activated Ca(2+) channels (CRAC) would prevent sustained elevation of [Ca(2+)]i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca(2+) ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca(2+). Ca(2+) entry then occurred upon admission of Ca(2+) to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca(2+) entry in a concentration-dependent manner within the range of 1 to 50 μM (IC50 = 3.4 μM), but had little or no effect on the physiological Ca(2+) spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca(2+)]i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca(2+)]i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.
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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.