{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:45:45Z","timestamp":1787017545689,"version":"build-2736575974"},"reference-count":45,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p>\n                    Aberrant cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    flux in pancreatic acinar cells is critical to the pathological pancreatic zymogen activation observed in acute pancreatitis, but the downstream effectors are not known. In this study, we examined the role of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated protein phosphatase 2B (or calcineurin) in zymogen activation. Isolated pancreatic acinar cells were stimulated with supraphysiological caerulein (100 nM) with or without the calcineurin inhibitors FK506 or cell-permeable calcineurin inhibitory peptide (CiP). Chymotrypsin activity was measured as a marker of zymogen activation, and the percent amylase secretion was used as a measure of enzyme secretion. Cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    changes were recorded in acinar cells loaded with the intermediate Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -affinity dye fluo-5F using a scanning confocal microscope. A 50% reduction in chymotrypsin activity was observed after pretreatment with 1 \u03bcM FK506 or 10 \u03bcM CiP. These pretreatments did not affect amylase secretion or the rise in cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    after caerulein stimulation. These findings suggest that calcineurin mediates caerulein-induced intra-acinar zymogen activation but not enzyme secretion or the initial caerulein-induced cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signal.\n                  <\/jats:p>","DOI":"10.1152\/ajpgi.00500.2006","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T23:18:50Z","timestamp":1172791130000},"page":"G1594-G1599","source":"Crossref","is-referenced-by-count":53,"title":["Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin"],"prefix":"10.1152","volume":"292","author":[{"given":"Sohail Z.","family":"Husain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne M.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred S.","family":"Gorelick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Nathanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahsan U.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Blumenthal DK\n                      , Takio K, Hansen RS, Krebs EG.\n                      Dephosphorylation of cAMP-dependent protein kinase regulatory subunit (type II) by calmodulin-dependent protein phosphatase. Determinants of substrate specificity.\n                      J Biol Chem\n                      261\n                      : 8140\u20138145, 1986.","DOI":"10.1016\/S0021-9258(19)83888-7"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.08.084"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199609263351302"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00334.2004"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90287-M"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.2174\/0929867003374723"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1995.01430010066013"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-14-05151.1998"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00281.2005"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1996.271.1.G20"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Groblewski GE\n                      , Wagner AC, Williams JA.\n                      Cyclosporin A inhibits Ca\n                      2+\n                      \/calmodulin-dependent protein phosphatase and secretion in pancreatic acinar cells.\n                      J Biol Chem\n                      269\n                      : 15111\u201315117, 1994.","DOI":"10.1016\/S0021-9258(17)36580-8"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.35.22738"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202929200"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00088.2003"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.2.G352"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503215102"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.2.242"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1007\/BF02358370"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.2174\/1568007033482878"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64515-4"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00388.2001"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1038\/nri1632"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1080\/110241500750008501"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207454200"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702471"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.5.G999"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1485"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.06.024"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.24.13126"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.4.1483"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.276.4.G835"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00534.2003"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704429"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00111.2003"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(97)00146-6"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1097\/01.mol.0000169352.35642.06"},{"key":"R38","unstructured":"Steer ML\n                      , Saluja AK.\n                      Experimental acute pancreatitis: studies of the early events that lead to cell injury. 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Philadelphia, PA: Lippincott, Williams & Wilkins, 2003, p. 2026\u20132060."},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5412.339"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13483.x"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-141"},{"key":"R45","unstructured":"Williams JA\n                      , Yule DI.\n                      Stimulus-secretion coupling in pancreatic acinar cells. In:\n                      Physiology of the Digestive Tract\n                      (4th ed.), edited by Johnson LR. New York: Academic, 2006, p. 1337\u20131369."}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00500.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T05:48:54Z","timestamp":1628488134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00500.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1152\/ajpgi.00500.2006"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00500.2006","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6]]}}}