ArticleThe Journal of biological chemistry2011
Ethanol enhances carbachol-induced protease activation and accelerates Ca2+ waves in isolated rat pancreatic acini.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis.Biomedicines · 2022Review
- Recent Advances in Understanding the Complexity of Alcohol-Induced Pancreatic Dysfunction and Pancreatitis Development.Biomolecules · 2020Review
- Genetics, Cell Biology, and Pathophysiology of Pancreatitis.Gastroenterology · 2019Review
- Depletion of the membrane-fusion regulator Munc18c attenuates caerulein hyperstimulation-induced pancreatitis.The Journal of biological chemistry · 2018Article
- Article
- Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2016Review
- The ryanodine receptor is expressed in human pancreatic acinar cells and contributes to acinar cell injury.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Cluster of differentiation 38 (CD38) mediates bile acid-induced acinar cell injury and pancreatitis through cyclic ADP-ribose and intracellular calcium release.The Journal of biological chemistry · 2013Article
- Pancreatic acinar cell nuclear factor κB activation because of bile acid exposure is dependent on calcineurin.The Journal of biological chemistry · 2013Article
- Preparation of pancreatic acinar cells for the purpose of calcium imaging, cell injury measurements, and adenoviral infection.Journal of visualized experiments : JoVE · 2013Article
- Effects of oxidative alcohol metabolism on the mitochondrial permeability transition pore and necrosis in a mouse model of alcoholic pancreatitis.Gastroenterology · 2013Article
- Bile acids induce pancreatic acinar cell injury and pancreatitis by activating calcineurin.The Journal of biological chemistry · 2013Article
- Raf-1 kinase inhibitory protein (RKIP) mediates ethanol-induced sensitization of secretagogue signaling in pancreatic acinar cells.The Journal of biological chemistry · 2012Article
- Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Article
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Authors and funding
8 authors.
Funding
Abstract
Alcohol abuse is a leading cause of pancreatitis, accounting for 30% of acute cases and 70-90% of chronic cases, yet the mechanisms leading to alcohol-associated pancreatic injury are unclear. An early and critical feature of pancreatitis is the aberrant signaling of Ca(2+) within the pancreatic acinar cell. An important conductor of this Ca(2+) is the basolaterally localized, intracellular Ca(2+) channel ryanodine receptor (RYR). In this study, we examined the effect of ethanol on mediating both pathologic intra-acinar protease activation, a precursor to pancreatitis, as well as RYR Ca(2+) signals. We hypothesized that ethanol sensitizes the acinar cell to protease activation by modulating RYR Ca(2+). Acinar cells were freshly isolated from rat, pretreated with ethanol, and stimulated with the muscarinic agonist carbachol (1 μM). Ethanol caused a doubling in the carbachol-induced activation of the proteases trypsin and chymotrypsin (p < 0.02). The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chymotrypsin activity by ethanol (p < 0.005 for both proteases). Further, ethanol accelerated the speed of the apical to basolateral Ca(2+) wave from 9 to 18 μm/s (p < 0.0005; n = 18-22 cells/group); an increase in Ca(2+) wave speed was also observed with a change from physiologic concentrations of carbachol (1 μM) to a supraphysiologic concentration (1 mM) that leads to protease activation. Dantrolene abrogated the ethanol-induced acceleration of wave speed (p < 0.05; n = 10-16 cells/group). Our results suggest that the enhancement of pathologic protease activation by ethanol is dependent on the RYR and that a novel mechanism for this enhancement may involve RYR-mediated acceleration of Ca(2+) waves.
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