2020
TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Gorelick F, Nathanson MH. TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells. Journal Of Clinical Investigation 2020, 130: 2199-2201. PMID: 32281947, PMCID: PMC7190901, DOI: 10.1172/jci136525.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsCalcium signalingAcinar cellsPlasma membrane calcium channelsGenetic deletion modelsMembrane calcium channelsCytosolic calcium levelsCell culture systemDeletion modelTransient receptor potential vanilloidPathogenesis of pancreatitisSignalingCulture systemCellsPathwayStimulation pathwayCalcium channels
2012
Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells
Kolodecik TR, Shugrue CA, Thrower EC, Levin LR, Buck J, Gorelick FS. Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells. PLOS ONE 2012, 7: e41320. PMID: 22844459, PMCID: PMC3402497, DOI: 10.1371/journal.pone.0041320.Peer-Reviewed Original ResearchConceptsProtein kinase AActivation of SACZymogen activationPancreatic acinar cellsSpecific subcellular domainsAcinar cellsActivation of zymogensCerulein-treated cellsSubcellular domainsDownstream targetsKinase ASAC activitySAC inhibitorAdenylyl cyclaseDistinct mechanismsAdenylyl cyclase inhibitorElevates levelsApical regionAmylase secretionCellsActivationAcinar cell vacuolizationCAMPCAMP accumulationCell vacuolization
2009
Protein Kinase C &dgr;-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic Acini
Thrower EC, Wang J, Cheriyan S, Lugea A, Kolodecik TR, Yuan J, Reeve JR, Gorelick FS, Pandol SJ. Protein Kinase C &dgr;-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic Acini. Pancreas 2009, 38: 930-935. PMID: 19752773, PMCID: PMC2767410, DOI: 10.1097/mpa.0b013e3181b8476a.Peer-Reviewed Original ResearchMeSH KeywordsAcetophenonesAmylasesAnimalsBenzopyransCalcium-Calmodulin-Dependent Protein KinasesCells, CulturedCholecystokininDose-Response Relationship, DrugEnzyme InhibitorsImmunoblottingIndolesMaleMaleimidesMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPancreasPeptide FragmentsProtein Kinase C-deltaRatsRats, Sprague-DawleyTrypsinogen
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
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 processing
1996
Effect of ethanol on cholecystokinin-stimulated zymogen conversion in pancreatic acinar cells
Katz M, Carangelo R, Miller LJ, Gorelick F. Effect of ethanol on cholecystokinin-stimulated zymogen conversion in pancreatic acinar cells. American Journal Of Physiology 1996, 270: g171-g175. PMID: 8772515, DOI: 10.1152/ajpgi.1996.270.1.g171.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsEffects of ethanolAbility of ethanolAcinar cellsHigh dosesLow dose cholecystokininCholecystokinin receptor antagonistDose of ethanolReceptor antagonistCholecystokininSmall intestineCholecystokinin receptorsEthanol treatmentActive formCarbamylcholineZymogen conversionIntracellular conversionDosesPancreatic zymogensCellsAntagonistDoseIntestine
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 concentrationsAciniCellsActivation
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 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
1988
Development of Secretagogue Responsiveness in the Pancreas
Jamieson JD, Gorelick FS, Chang A. Development of Secretagogue Responsiveness in the Pancreas. Scandinavian Journal Of Gastroenterology 1988, 23: 98-103. PMID: 2852401, DOI: 10.3109/00365528809095920.Peer-Reviewed Original ResearchConceptsSecretory pathwaySecretory proteinsPancreatic acinar cellsEpithelial cell polarityDependent protein kinase IIRegulated secretory pathwayConstitutive secretory pathwayAcinar cellsProtein kinase IICell polarityMembrane proteinsPhosphorylated substratesRegulated secretionBasolateral domainCell biologyPlasmalemmal domainsPlasma membraneKinase IISecond messengerSecretagogue responsivenessFunctional specializationProteinEpithelial cellsPathwayZymogen granules