2014
Low pH enhances connexin32 degradation in the pancreatic acinar cell
Reed AM, Kolodecik T, Husain SZ, Gorelick FS. Low pH enhances connexin32 degradation in the pancreatic acinar cell. AJP Gastrointestinal And Liver Physiology 2014, 307: g24-g32. PMID: 24812055, PMCID: PMC4080162, DOI: 10.1152/ajpgi.00010.2014.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsGap junctionsGap junctional intercellular communicationIntercellular communicationRat pancreatic acinar cellsPredominant gap junction proteinExtracellular pHAcute pancreatitisJunctional intercellular communicationClinical conditionsGap junction proteinJunction proteinsGap junctional intracellular communicationAutophagic pathwayFirst evidenceCellsIntracellular communicationConnexin32Pancreatitis
2010
Low Extracellular pH Induces Damage in the Pancreatic Acinar Cell by Enhancing Calcium Signaling*
Reed AM, Husain SZ, Thrower E, Alexandre M, Shah A, Gorelick FS, Nathanson MH. Low Extracellular pH Induces Damage in the Pancreatic Acinar Cell by Enhancing Calcium Signaling*. Journal Of Biological Chemistry 2010, 286: 1919-1926. PMID: 21084290, PMCID: PMC3023488, DOI: 10.1074/jbc.m110.158329.Peer-Reviewed Original ResearchConceptsPathogenesis of pancreatitisAcinar cellsRyR inhibitorsLow pHeDevelopment of pancreatitisRyanodine receptor inhibitorPancreatic acinar cellsReceptor inhibitorsClinical conditionsCellular injuryPancreatitisBasolateral regionExocrine pancreasPancreatitis responsesInjurious effectsCalcium signalingPathogenesisInduces damageInhibitorsCellsRyRsInjuryEarly stepsPancreasSensitization
2009
Reducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats
Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, Thrower EC, Gorelick FS. Reducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats. Gastroenterology 2009, 137: 1083-1092. PMID: 19454288, PMCID: PMC2736307, DOI: 10.1053/j.gastro.2009.05.041.Peer-Reviewed Original ResearchConceptsAcinar cellsAcute pancreatitisPancreatic acinar cellsSecretagogue-induced pancreatitisAcid loadAcid challengeAcute acid loadKey early eventPancreatic edemaClinical studiesCell injuryPancreatitisAmylase secretionIsolated aciniAbstractTextPhe effectTrypsinogen activationInjuryPancreatitis responsesZymogen activationAIMSEarly eventsRatsActivationRelevant concentrations
2008
Prevention of post-ERCP pancreatitis: a little antacid might go a long way
Nagar AB, Gorelick F. Prevention of post-ERCP pancreatitis: a little antacid might go a long way. Gut 2008, 57: 1492. PMID: 18941003, DOI: 10.1136/gut.2008.157289.Peer-Reviewed Original Research
2006
Vacuolar adenosine triphosphatase and pancreatic acinar cell function
Gorelick FS, Shugrue CA, Kolodecik TR, Thrower EC. Vacuolar adenosine triphosphatase and pancreatic acinar cell function. Journal Of Gastroenterology And Hepatology 2006, 21: s18-s21. PMID: 16958663, DOI: 10.1111/j.1440-1746.2006.04576.x.Peer-Reviewed Original Research
2004
Vacuolar ATPase Regulates Zymogen Activation in Pancreatic Acini*
Waterford SD, Kolodecik TR, Thrower EC, Gorelick FS. Vacuolar ATPase Regulates Zymogen Activation in Pancreatic Acini*. Journal Of Biological Chemistry 2004, 280: 5430-5434. PMID: 15582989, PMCID: PMC2846595, DOI: 10.1074/jbc.m413513200.Peer-Reviewed Original ResearchMeSH KeywordsAmylasesAnimalsCalciumCarbacholCell MembraneCells, CulturedCeruletideChloroquineChymotrypsinEnzyme ActivationEnzyme PrecursorsHydrogen-Ion ConcentrationMacrolidesMaleMonensinPancreasProtein SubunitsProtein TransportRatsRats, Sprague-DawleySolubilityThapsigarginTrypsinVacuolar Proton-Translocating ATPasesConceptsPancreatic acinar cellsSupramaximal concentrationsPancreatic aciniAcinar cellsVacuolar ATPase inhibitor bafilomycinConcentration-dependent mannerAcute pancreatitisEffects of agentsATPase inhibitor bafilomycinConcentration-dependent translocationWeak base chloroquineCaerulein stimulationIntracellular pHConcanamycin AChymotrypsin activationActivationBase chloroquineV-ATPase activationInhibitor bafilomycin
2003
Alcohol and Zymogen Activation in the Pancreatic Acinar Cell
Gorelick FS. Alcohol and Zymogen Activation in the Pancreatic Acinar Cell. Pancreas 2003, 27: 305-310. PMID: 14576492, DOI: 10.1097/00006676-200311000-00006.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsSupraphysiologic concentrationsAcute pancreatitisAbility of alcoholMechanism of sensitizationEarly featureIsolated aciniCholecystokininPancreatic aciniInduced activationSensitizationPancreatitisAciniZymogen activationActivationLysosomal markersGranule compartmentCellsActivation of zymogens
2000
Cytoplasmic Vacuole Generation in Rat Isolated Pancreatic Acini Under Secretagogue Hyperstimulation Is Associated with Intracellular Acidification
Otani T, Gorelick F. Cytoplasmic Vacuole Generation in Rat Isolated Pancreatic Acini Under Secretagogue Hyperstimulation Is Associated with Intracellular Acidification. Pancreas 2000, 21: 105-107. PMID: 10881943, DOI: 10.1097/00006676-200007000-00062.Peer-Reviewed Original ResearchAnimalsCarbacholCytoplasmHydrogen-Ion ConcentrationMaleMicroscopy, ElectronPancreasRatsRats, Sprague-DawleyVacuolesEARLY TRYPSINOGEN ACTIVATION IN ACUTE PANCREATITIS
Lerch M, Gorelick F. EARLY TRYPSINOGEN ACTIVATION IN ACUTE PANCREATITIS. Medical Clinics Of North America 2000, 84: 549-563. PMID: 10872413, DOI: 10.1016/s0025-7125(05)70239-x.Peer-Reviewed Original ResearchMeSH KeywordsCalcium SignalingEndopeptidasesEnzyme ActivationGenetic Predisposition to DiseaseHumansHydrogen-Ion ConcentrationPancreasPancreatitis, Acute NecrotizingTrypsinogen
1999
Mechanisms of intracellular zymogen activation
Gorelick F, Otani T. Mechanisms of intracellular zymogen activation. Best Practice & Research Clinical Gastroenterology 1999, 13: 227-240. PMID: 11030603, DOI: 10.1053/bega.1999.0021.Peer-Reviewed Original ResearchConceptsTrypsinogen activation peptideAcinar cellsZymogen processingDistinct subcellular compartmentsZymogen activationSerine proteasesIntracellular serine proteaseIntracellular zymogen activationCaerulein-induced pancreatitisAcinar cell compartmentPancreatic acinar cellsAcute pancreatitisSubcellular compartmentsHuman pancreatitisPancreatitisExperimental pancreatitisSupramaximal concentrationsHereditary pancreatitisLow-pH compartmentsPancreatic aciniTrypsinogen activationTrypsinogen processingGenetic diseasesCell pathwaysIntracellular activation
1993
Influence of Chloroquine on Diet-Induced Pancreatitis
Leach S, Bilchik A, Karapetian O, Gorelick F, Modlin I. Influence of Chloroquine on Diet-Induced Pancreatitis. Pancreas 1993, 8: 64-69. PMID: 7678327, DOI: 10.1097/00006676-199301000-00013.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAmylasesAnimalsChloroquineCholineDietEthionineFemaleHydrogen-Ion ConcentrationMicePancreasPancreatitisSubcellular FractionsTrypsinConceptsHigh-dose chloroquineAcidic subcellular compartmentsDiet-induced pancreatitisEthionine-supplemented dietRegular laboratory chowYoung female miceInfluence of chloroquineIntracellular zymogen activationCDE dietAcute pancreatitisContinuous infusionFemale miceLaboratory chowControl animalsPancreatitisExperimental pancreatitisAdditional potential effectsLow-pH compartmentsTrypsinogen contentPancreatic aciniChloroquineAcinar cellsTryptic activityAnimalsDigestive zymogens
1992
Intracellular proteolysis of pancreatic zymogens.
Gorelick FS, Modlin IM, Leach SD, Carangelo R, Katz M. Intracellular proteolysis of pancreatic zymogens. The Yale Journal Of Biology And Medicine 1992, 65: 407-20; discussion 437-40. PMID: 1340058, PMCID: PMC2589730.Peer-Reviewed Original ResearchAnimalsBenzamidinesBiological TransportCarbacholCarboxypeptidase BCarboxypeptidasesCarboxypeptidases ACholecystokininChymotrypsinogenCysteine Proteinase InhibitorsEnzyme ActivationEnzyme PrecursorsHydrogen-Ion ConcentrationLeucineModels, BiologicalPancreasPancreatitisProtein Processing, Post-TranslationalTime FactorsTrypsin Inhibitors
1991
Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin.
Leach SD, Modlin IM, Scheele GA, Gorelick FS. Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin. Journal Of Clinical Investigation 1991, 87: 362-366. PMID: 1985109, PMCID: PMC295064, DOI: 10.1172/jci114995.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarboxypeptidasesCarboxypeptidases ACholecystokininEnzyme ActivationEnzyme PrecursorsHydrogen-Ion ConcentrationMalePancreasProtease InhibitorsRatsRats, Inbred StrainsConceptsPancreatic aciniIntracellular activationCysteine protease inhibitor E64Digestive zymogensDose of cholecystokininRat pancreatic aciniProtease inhibitor E64Acute pancreatitisCholecystokininHigh dosesSerine protease activityAcidic subcellular compartmentsWeak base chloroquineImmunologic techniquesInhibitor E64Protonophore monensinPancreatitisIncubation mediumAciniBase chloroquineActivationIntracellular sitesProtease inhibitor benzamidineCell pelletsElectrophoretic mobility
1990
Rabbit ileal villus cell brush border Na+/H+ exchange is regulated by Ca2+/calmodulin-dependent protein kinase II, a brush border membrane protein.
Cohen ME, Reinlib L, Watson AJ, Gorelick F, Rys-Sikora K, Tse M, Rood RP, Czernik AJ, Sharp GW, Donowitz M. Rabbit ileal villus cell brush border Na+/H+ exchange is regulated by Ca2+/calmodulin-dependent protein kinase II, a brush border membrane protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 8990-8994. PMID: 2174171, PMCID: PMC55086, DOI: 10.1073/pnas.87.22.8990.Peer-Reviewed Original ResearchConceptsDependent protein kinase IIProtein kinase IIKinase IIMembrane proteinsSynapsin IDependent protein kinase activityDependent protein kinaseBrush border membranePhosphorylation of sitesProtein kinase activityInhibitor peptideCaM kinase IIBrush border membrane proteinsBorder membraneSpecific inhibitor peptidePhosphopeptide mappingBrush borderProtein kinaseMicrovillus membrane proteinsKinase activityIleal brush-border membraneVillus cell brush border membraneApical membraneKinaseVesicle preparations