2012
Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses
Alexandre M, Uduman AK, Minervini S, Raoof A, Shugrue CA, Akinbiyi EO, Patel V, Shitia M, Kolodecik TR, Patton R, Gorelick FS, Thrower EC. Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses. AJP Gastrointestinal And Liver Physiology 2012, 303: g696-g704. PMID: 22837343, PMCID: PMC3468532, DOI: 10.1152/ajpgi.00138.2012.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAcetylcholine receptorsCigarette smoke toxinsParameters of pancreatitisPancreatitis responsesTobacco carcinogen 4Acinar cell responsesRat pancreatic aciniSmoke toxinsAcute pancreatitisCigarette smokingIntraperitoneal injectionAcinar cell preparationsClinical studiesLong-term effectsCarcinogen 4Pancreatitis modelAdrenergic receptorsReceptor typesCell responsesTobacco toxinsPyknotic nucleiNNKPancreatic aciniPancreatitis
2008
Protein kinase C in the pancreatic acinar cell
Gorelick F, Pandol S, Thrower E. Protein kinase C in the pancreatic acinar cell. Journal Of Gastroenterology And Hepatology 2008, 23: s37-s41. PMID: 18336661, DOI: 10.1111/j.1440-1746.2007.05282.x.Peer-Reviewed Original ResearchConceptsProtein kinase CKinase CCell-free reconstitution systemPancreatic acinar cellsAcinar cellsPathological responseSpecific PKC isoformsPathogenesis of pancreatitisReconstitution systemCellular eventsPKC isoformsActivation of proteasesApical secretionProtease activationCell eventsInflammatory mediatorsAcute pancreatitisPathological activationSupraphysiological concentrationsPancreatitisPathological effectsPancreatic aciniCholecystokininCellsActivation
2007
Cyclic AMP-dependent protein kinase and Epac mediate cyclic AMP responses in pancreatic acini
Chaudhuri A, Husain SZ, Kolodecik TR, Grant WM, Gorelick FS. Cyclic AMP-dependent protein kinase and Epac mediate cyclic AMP responses in pancreatic acini. AJP Gastrointestinal And Liver Physiology 2007, 292: g1403-g1410. PMID: 17234888, PMCID: PMC2975017, DOI: 10.1152/ajpgi.00478.2005.Peer-Reviewed Original ResearchConceptsProtein kinaseZymogen activationCAMP-dependent protein kinaseStimulation of PKACyclic AMP-dependent protein kinasePancreatic acinar cellsAMP-dependent protein kinaseApical actin cytoskeletonCAMP-binding proteinsRole of PKAMuscarinic agonist carbacholIntracellular zymogen activationSupraphysiological concentrationsCAMP-dependent pathwayActin cytoskeletonApical cytoskeletonPhenotypic responsesPKA responseAgonist carbacholCarbachol-induced activationAcinar cellsDecreased secretionEpacCAMP pathwayPancreatic acini
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 bafilomycinEffects of increased intracellular cAMP on carbachol-stimulated zymogen activation, secretion, and injury in the pancreatic acinar cell
Chaudhuri A, Kolodecik TR, Gorelick FS. Effects of increased intracellular cAMP on carbachol-stimulated zymogen activation, secretion, and injury in the pancreatic acinar cell. AJP Gastrointestinal And Liver Physiology 2004, 288: g235-g243. PMID: 15458924, PMCID: PMC2975016, DOI: 10.1152/ajpgi.00334.2004.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsSecretion of amylaseAcinar cellsCell injuryIntracellular cAMPForms of pancreatitisParameters of injuryAcinar cell injuryCholinergic agonist carbacholEnzyme secretionRat pancreatic acinar cellsAcute pancreatitisZymogen activationAgonist carbacholSupraphysiological concentrationsCellular injuryCarbacholInjuryPancreatic aciniCAMP productionUnstimulated aciniSecretionCellular cAMPPhysiological concentrationsPancreatitis
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 zymogensEffect of ligands that increase cAMP on caerulein-induced zymogen activation in pancreatic acini
Lu Z, Kolodecik TR, Karne S, Nyce M, Gorelick F. Effect of ligands that increase cAMP on caerulein-induced zymogen activation in pancreatic acini. AJP Gastrointestinal And Liver Physiology 2003, 285: g822-g828. PMID: 12881228, PMCID: PMC2830556, DOI: 10.1152/ajpgi.00213.2003.Peer-Reviewed Original ResearchConceptsCCK analogue caeruleinEffect of CCKAcinar cellsSupraphysiological concentrationsPancreatic aciniCell cAMP levelsRat pancreatic aciniRp-8-BrPancreatic acinar cellsPathological activationCell-permeable cAMP analogCAMP levelsPhysiological concentrationsPancreatitisCell cAMPCCKZymogen activationActivationCAMP analogPhysiological ligandsAciniCells
2002
Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells
Lu Z, Karne S, Kolodecik T, Gorelick FS. Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2002, 282: g501-g507. PMID: 11842000, PMCID: PMC2830557, DOI: 10.1152/ajpgi.00388.2001.Peer-Reviewed Original Research
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
1998
Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury
Grady T, Mah’Moud M, Otani T, Rhee S, Lerch MM, Gorelick FS. Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury. American Journal Of Physiology 1998, 275: g1010-g1017. PMID: 9815031, DOI: 10.1152/ajpgi.1998.275.5.g1010.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsCellular injuryForms of pancreatitisAcinar cell injuryTrypsinogen activation peptideSecretagogue treatmentPathological activationCell injuryInjuryIsolated aciniHyperstimulationBombesin treatmentPancreatic aciniTrypsinogen processingImmunofluorescence studiesBombesin stimulationAciniCA1TreatmentDigestive zymogensActivationCellsZymogen activationZymogen processingTelenzepine-sensitive muscarinic receptors on rat pancreatic acinar cells
Schmid S, Modlin I, Tang L, Stoch A, Rhee S, Nathanson M, Scheele G, Gorelick F. Telenzepine-sensitive muscarinic receptors on rat pancreatic acinar cells. American Journal Of Physiology 1998, 274: g734-g741. PMID: 9575856, DOI: 10.1152/ajpgi.1998.274.4.g734.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAmylase secretionRat pancreatic acinar cellsMuscarinic receptorsAcinar cellsDifferent muscarinic receptor antagonistsM2 antagonist methoctramineMaximal amylase secretionMuscarinic receptor antagonistIsolated rat pancreatic aciniRat pancreatic aciniAntagonist methoctramineM3 subtypeM1 antagonistMuscarinic subtypesReceptor antagonistZymogen processingAntagonist sensitivityPancreatic aciniSecretionAntagonistSubtypesPotent inhibitorReceptorsDistinct patterns
1997
Distribution of a Synthetic Protease Inhibitor in Rat Pancreatic Acini After Supramaximal Secretagogue Stimulation
Otani T, Atomi Y, Kuroda A, Muto T, Tamura M, Fukuda S, Akao S, Gorelick F. Distribution of a Synthetic Protease Inhibitor in Rat Pancreatic Acini After Supramaximal Secretagogue Stimulation. Pancreas 1997, 14: 142-149. PMID: 9057186, DOI: 10.1097/00006676-199703000-00006.Peer-Reviewed Original ResearchConceptsAcinar cellsPancreatic aciniProtease inhibitorsLow molecular weight protease inhibitorSynthetic protease inhibitorLarge cytoplasmic vacuolesIsolated pancreatic aciniRat pancreatic aciniAcute pancreatitisWeight protease inhibitorsZymogen granulesCerulein treatmentE3123Supramaximal secretagogue stimulationVivo modelElectron microscopic autoradiographyBeneficial effectsMin of incubationUnstimulated controlsMicroscopic autoradiographyInhibition of proteasesCytoplasmic vacuolesAciniPancreatitisFormation of vacuoles
1993
Characterization of cAMP‐dependent protein kinase activation by CCK in rat pancreas
Marino C, Leach S, Schaefer J, Miller L, Gorelick F. Characterization of cAMP‐dependent protein kinase activation by CCK in rat pancreas. FEBS Letters 1993, 316: 48-52. PMID: 7678554, PMCID: PMC2830555, DOI: 10.1016/0014-5793(93)81734-h.Peer-Reviewed Original ResearchConceptsCAMP-dependent protein kinase activityProtein kinase activityKinase activityCAMP second messenger cascadeCAMP-dependent protein kinase activationProtein kinase activationSecond messenger cascadesCellular cAMP levelsKinase activationCAMP cascadeTreatment of aciniMessenger cascadesCellular cAMPCAMP levelsEnzyme secretionCascadeNew sensitive assayRat pancreatic aciniSensitive assayPancreatic aciniActivityHigh concentrationsAciniCellsActivationInfluence 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 ResearchConceptsHigh-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
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 ResearchConceptsPancreatic 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