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Disturbed intracellular Ca<jats:sup>2+<\/jats:sup> signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra\u2010acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca<jats:sup>2+<\/jats:sup> overload is a promising therapeutic target. Transient receptor potential melastatin 2 (TRPM2) is a non\u2010selective cation channel that has recently emerged as an important contributor to oxidative\u2010stress\u2010induced cellular Ca<jats:sup>2+<\/jats:sup> overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> treatment. TRPM2 activity was found to contribute to bile acid\u2010induced extracellular Ca<jats:sup>2+<\/jats:sup> influx in acinar cells, but did not have the same effect in ductal cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells compared to isolated ducts, which can explain the difference between acinar and ductal cells. This activity promoted acinar cell necrosis <jats:italic>in vitro<\/jats:italic> independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile\u2010acid\u2010induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein\u2010induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp279047","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T17:26:57Z","timestamp":1578590817000},"page":"1253-1270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["TRPM2\u2010mediated extracellular Ca<sup>2+<\/sup> entry promotes acinar cell necrosis in biliary acute pancreatitis"],"prefix":"10.1113","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-3857","authenticated-orcid":false,"given":"J\u00falia","family":"Fanczal","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Pallagi","sequence":"additional","affiliation":[{"name":"First Department of Internal 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