{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":46,"searchCount":0},"additional":{"submitter":["Reed AM"],"funding":["NIDDK NIH HHS"],"pagination":["1919-26"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3023488"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["286(3)"],"pubmed_abstract":["Low extracellular pH (pHe) occurs in a number of clinical conditions and sensitizes to the development of pancreatitis. The mechanisms responsible for this sensitization are unknown. Because abnormal Ca(2+) signaling underlies many of the early steps in the pathogenesis of pancreatitis, we evaluated the effect of decreasing pHe from 7.4 to 7.0 on Ca(2+) signals in the acinar cell. Low pHe significantly increased the amplitude of cerulein-induced Ca(2+) signals. The enhancement in amplitude was localized to the basolateral region of the acinar cell and was reduced by pretreatment with ryanodine receptor (RYR) inhibitors. Because basolateral RYRs also have been implicated in the pathogenesis of pancreatitis, we evaluated the effects of RYR inhibitors on pancreatitis responses in acidic conditions. RYR inhibitors significantly reduced the sensitizing effects of low pHe on zymogen activation and cellular injury. These findings suggest that enhanced RYR-mediated Ca(2+) signaling in the basolateral region of the acinar cell is responsible for the injurious effects of low pHe on the exocrine pancreas."],"journal":["The Journal of biological chemistry"],"pubmed_title":["Low extracellular pH induces damage in the pancreatic acinar cell by enhancing calcium signaling."],"pmcid":["PMC3023488"],"funding_grant_id":["R01 DK054021","R01 DK061747","P01 DK057751","DK61747","DK57751","K08 DK090104-01","K08 DK068116","K08 DK090104","T32 DK007356-31","DK45710","R01 DK54021","DK34989","T32 DK007356","K08 DK68116","R01 DK093491","R03 DK078707","P30 DK034989","R01 DK083327","R01 DK045710"],"pubmed_authors":["Husain SZ","Thrower E","Shah A","Alexandre M","Gorelick FS","Nathanson MH","Reed AM"],"view_count":["46"],"additional_accession":[]},"is_claimable":false,"name":"Low extracellular pH induces damage in the pancreatic acinar cell by enhancing calcium signaling.","description":"Low extracellular pH (pHe) occurs in a number of clinical conditions and sensitizes to the development of pancreatitis. The mechanisms responsible for this sensitization are unknown. Because abnormal Ca(2+) signaling underlies many of the early steps in the pathogenesis of pancreatitis, we evaluated the effect of decreasing pHe from 7.4 to 7.0 on Ca(2+) signals in the acinar cell. Low pHe significantly increased the amplitude of cerulein-induced Ca(2+) signals. The enhancement in amplitude was localized to the basolateral region of the acinar cell and was reduced by pretreatment with ryanodine receptor (RYR) inhibitors. Because basolateral RYRs also have been implicated in the pathogenesis of pancreatitis, we evaluated the effects of RYR inhibitors on pancreatitis responses in acidic conditions. RYR inhibitors significantly reduced the sensitizing effects of low pHe on zymogen activation and cellular injury. These findings suggest that enhanced RYR-mediated Ca(2+) signaling in the basolateral region of the acinar cell is responsible for the injurious effects of low pHe on the exocrine pancreas.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Jan","modification":"2024-11-14T13:55:15.852Z","creation":"2019-03-27T00:38:15Z"},"accession":"S-EPMC3023488","cross_references":{"pubmed":["21084290"],"doi":["10.1074/jbc.M110.158329","10.1074/jbc.m110.158329"]}}