2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissue
2013
Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine
Rogers AC, Huetter L, Hoekstra N, Collins D, Collaco A, Baird AW, Winter DC, Ameen N, Geibel JP, Kopic S. Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine. PLOS ONE 2013, 8: e69050. PMID: 23935921, PMCID: PMC3728293, DOI: 10.1371/journal.pone.0069050.Peer-Reviewed Original ResearchConceptsIntestinal chloride secretionCholera toxinChloride secretionPharmacological activationFluid accumulationColonic cryptsSupplemental treatment strategyAcute diarrheal illnessChloride effluxCystic fibrosis transmembrane conductance regulatorExcised intestinal segmentsRat colonic cryptsMurine colonic mucosaMucosal sheetsDiarrheal illnessIntestinal loopsEnterotoxigenic diarrheaColonic mucosaTreatment strategiesIntestinal segmentsUssing chambersAMPK activator AICARMurine intestineTissue levelsMetformin
2011
Hypoxia Inhibits Colonic Ion Transport via Activation of AMP Kinase
Collins D, Kopic S, Bachlechner J, Ritter M, Winter DC, Geibel JP. Hypoxia Inhibits Colonic Ion Transport via Activation of AMP Kinase. Annals Of Surgery 2011, 254: 957-963. PMID: 21562404, DOI: 10.1097/sla.0b013e31821d477f.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorChloride secretionMucosal hypoxiaAcute hypoxiaColonic electrolyte transportColonic mucosal functionIschemic intestinal injuryElectrogenic chloride secretionColonic ion transportPotential therapeutic targetHuman colonic mucosaIntracellular chloride concentrationRat colonic cryptsEpithelial ion transportFibrosis transmembrane conductance regulatorIschemic colitisIntestinal injuryColonic obstructionInhibition of CFTRMucosal functionAnastomotic failureAcute effectsColonic mucosaAdaptive cellular responseTransmembrane conductance regulatorAngiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts
Wagner CA, Mohebbi N, Uhlig U, Giebisch GH, Breton S, Brown D, Geibel JP. Angiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts. Cellular Physiology And Biochemistry 2011, 28: 513-520. PMID: 22116365, PMCID: PMC3709473, DOI: 10.1159/000335112.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsAnion Transport ProteinsBicarbonatesCell MembraneChloridesColchicineHydrogen-Ion ConcentrationImmunohistochemistryKidney CortexKidney Tubules, CollectingMacrolidesMaleMiceMice, Inbred C57BLReceptors, AngiotensinSaralasinSodiumSulfate TransportersVacuolar Proton-Translocating ATPasesConceptsCNT/CCDAngiotensin IICortical collecting ductsBicarbonate secretionChloride absorptionCollecting ductsType 1 angiotensin II receptorAngiotensin II stimulatesAngiotensin II receptorsAcid-base statusConnecting tubuleATPase activityII receptorsSpecific subtypesNephron segmentsIndependent intracellularAcid extrusionType BSecretionTubulesDuct systemDuctPendrinPresent studyCellsCalcium-Modulated Chloride Pathways Contribute to Chloride Flux in Murine Cystic Fibrosis-Affected Macrophages
Shenoy A, Kopic S, Murek M, Caputo C, Geibel JP, Egan ME. Calcium-Modulated Chloride Pathways Contribute to Chloride Flux in Murine Cystic Fibrosis-Affected Macrophages. Pediatric Research 2011, 70: 447-452. PMID: 21796019, PMCID: PMC3189336, DOI: 10.1203/pdr.0b013e31822f2448.Peer-Reviewed Original ResearchConceptsCystic fibrosisWT macrophagesCF macrophagesExtracellular Ca2CAMP-activated chloride channelCystic fibrosis transmembrane conductance regulator (CFTR) proteinContribution of CFTRIon transport abnormalitiesResult of mutationsContribution of calciumRegulator proteinRobust inflammationChronic infectionMacrophage dysfunctionMacrophage functionIntracellular Ca2Transport abnormalitiesMacrophagesChloride channelsMethoxy-quinolinium bromideCFTRinh-172Fluorescent indicator dyesFibrosisPathwayCFTRThe flavonone naringenin inhibits chloride secretion in isolated colonic epithelia
Collins D, Kopic S, Geibel JP, Hogan AM, Medani M, Baird AW, Winter DC. The flavonone naringenin inhibits chloride secretion in isolated colonic epithelia. European Journal Of Pharmacology 2011, 668: 271-277. PMID: 21762688, DOI: 10.1016/j.ejphar.2011.06.052.Peer-Reviewed Original ResearchConceptsHuman colonic mucosaChloride secretionAntisecretory actionColonic mucosaCo-transporter inhibitorsEffect of naringeninIntracellular cAMP generationColonic cell lineAntisecretory effectColonic functionColorectal cancerProtective effectUssing chambersColonic epitheliumSecretory functionCAMP generationInhibitory actionBasolateral NKCC1Human colonRatsSecretionIntracellular acidificationConflicting resultsCell linesMucosa
2010
Update on the Mechanisms of Gastric Acid Secretion
Kopic S, Geibel JP. Update on the Mechanisms of Gastric Acid Secretion. Current Gastroenterology Reports 2010, 12: 458-464. PMID: 20821079, DOI: 10.1007/s11894-010-0137-9.Peer-Reviewed Original ResearchZinc Salts Provide a Novel, Prolonged and Rapid Inhibition of Gastric Acid Secretion
Kirchhoff P, Socrates T, Sidani S, Duffy A, Breidthardt T, Grob C, Viehl CT, Beglinger C, Oertli D, Geibel JP. Zinc Salts Provide a Novel, Prolonged and Rapid Inhibition of Gastric Acid Secretion. The American Journal Of Gastroenterology 2010, 106: 62. PMID: 20736941, DOI: 10.1038/ajg.2010.327.Peer-Reviewed Original ResearchConceptsProton pump inhibitorsGastric acid secretionAcid secretionRat gastric glandsRandomized cross-over studyIntact rat stomachAcid suppression therapyGastric glandsCross-over studyOnset of actionLong-term efficacyReturn of symptomsHealthy human volunteersSecretagogue-induced acid secretionStomach acid secretionProlonged therapySuppression therapyIntragastric pHPump inhibitorsSingle doseWhole stomachLifetime prevalenceRat modelRat stomachFaster onsetEvidence for intestinal chloride secretion
Murek M, Kopic S, Geibel J. Evidence for intestinal chloride secretion. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2010, 95: 471-478. PMID: 20233891, DOI: 10.1113/expphysiol.2009.049445.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChloride ChannelsChloridesCLC-2 Chloride ChannelsCystic Fibrosis Transmembrane Conductance RegulatorDiarrheaEnterocytesHumansIntestinal AbsorptionIntestinal MucosaIntestinal SecretionsPotassium ChannelsSodium-Potassium-Chloride SymportersSodium-Potassium-Exchanging ATPaseTight JunctionsWater-Electrolyte BalanceCommentary on ‘Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof’
Kopic S, Murek M, Geibel JP. Commentary on ‘Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof’. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2010, 95: 484-485. PMID: 20233894, DOI: 10.1113/expphysiol.2009.051912.Peer-Reviewed Original Research
2007
SLC26A7 Can function as a chloride-loading mechanism in parietal cells
Kosiek O, Busque SM, Föller M, Shcheynikov N, Kirchhoff P, Bleich M, Muallem S, Geibel JP. SLC26A7 Can function as a chloride-loading mechanism in parietal cells. Pflügers Archiv - European Journal Of Physiology 2007, 454: 989-998. PMID: 17404755, DOI: 10.1007/s00424-007-0254-y.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnimalsAntiportersChloride-Bicarbonate AntiportersChloridesFluorescent Antibody TechniqueGastric AcidGastric MucosaImage Processing, Computer-AssistedIn Vitro TechniquesMaleOocytesParietal Cells, GastricPatch-Clamp TechniquesRatsRats, Sprague-DawleySodiumSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 2Sulfate TransportersXenopusConceptsParietal cellsXenopus laevis oocyte expression systemRat parietal cellsExpression of SLC26A7Rat gastric glandsAcid secretionOocyte expression systemNKCC inhibitorWestern blotHistamine stimulationPharmacological inhibitorsAcidic pHiGastric glandsDIDS concentrationExchanger AE2Subsequent readditionTransporter activityDisulfonic acidInhibitorsCellsSLC26A7InfluxImmunohistochemistrySecretagoguesUptake systemCharacteristics of rat downregulated in adenoma (rDRA) expressed in HEK 293 cells
Barmeyer C, Ye JH, Sidani S, Geibel J, Binder HJ, Rajendran VM. Characteristics of rat downregulated in adenoma (rDRA) expressed in HEK 293 cells. Pflügers Archiv - European Journal Of Physiology 2007, 454: 441-450. PMID: 17492310, DOI: 10.1007/s00424-007-0213-7.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmino Acid SequenceAnimalsAntiportersBase SequenceBicarbonatesCell LineChloridesCloning, MolecularColonDNA PrimersFatty Acids, VolatileHumansHydrogen-Ion ConcentrationIon TransportMolecular Sequence DataRatsRecombinant ProteinsSequence Homology, Amino AcidSulfate TransportersTransfectionConceptsRat distal colonDistal colonHEK-293 cellsExtracellular Cl- concentrationCrypt cellsMRNA expressionColonRatsDigestive tractCharacteristics of ratsAdenomasHigh rateDIDSCl- influxSurface cellsIntracellular acidApical membrane vesiclesCellsDisulfonic acidApical membraneCl- uptakePrior observationsUptakeLungJejunum
2005
Bicarbonate Secretion
Binder HJ, Rajendran V, Sadasivan V, Geibel JP. Bicarbonate Secretion. Journal Of Clinical Gastroenterology 2005, 39: s53-s58. PMID: 15758660, DOI: 10.1097/01.mcg.0000155521.81382.3a.Peer-Reviewed Original Research
2003
Characterization of Cl-HCO3 exchange in basolateral membrane of rat distal colon
Ikuma M, Geibel J, Binder HJ, Rajendran VM. Characterization of Cl-HCO3 exchange in basolateral membrane of rat distal colon. American Journal Of Physiology - Cell Physiology 2003, 285: c912-c921. PMID: 12826602, DOI: 10.1152/ajpcell.00396.2002.Peer-Reviewed Original ResearchConceptsRat distal colonCl-HCO3 exchangeDistal colonBasolateral membraneHalf-maximal inhibitory constantsBasolateral membrane vesiclesCl- channel blockerColonic epithelial cellsAbsence of HCO3Channel blockersRat colonic epithelial cellsCrypt preparationCrypt cellsExchange inhibitorCl-OH exchangeRemoval of ClColonEpithelial cellsAnion exchange inhibitorHCO3- gradientProtease inhibitorsK ionophorePresent studyInhibitory constantsProtease inhibitor cocktail
2001
Characterization of apical membrane Cl-dependent Na/H exchange in crypt cells of rat distal colon
Rajendran V, Geibel J, Binder H. Characterization of apical membrane Cl-dependent Na/H exchange in crypt cells of rat distal colon. AJP Gastrointestinal And Liver Physiology 2001, 280: g400-g405. PMID: 11171622, DOI: 10.1152/ajpgi.2001.280.3.g400.Peer-Reviewed Original ResearchConceptsRat distal colonNa/H exchangeCl- channel blockerDistal colonChannel blockersCrypt cellsIntracellular pH recoveryExchange inhibitor amilorideColonic epithelial cellsApical membrane vesiclesCrypt glandsHigh doseHOE 694NA depletionAcid loadExchange inhibitorInhibitor amiloridePH recoveryEpithelial cellsUptake 1NHE isoformsAnion exchange inhibitorBlockersColonNa uptakeNa+-dependent fluid absorption in intact perfused rat colonic crypts
Geibel J, Rajendran V, Binder H. Na+-dependent fluid absorption in intact perfused rat colonic crypts. Gastroenterology 2001, 120: 144-150. PMID: 11208723, DOI: 10.1053/gast.2001.20890.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnimalsBicarbonatesChloridesColonGanglionic StimulantsGlutamatesIn Vitro TechniquesIntestinal AbsorptionInulinIsotonic SolutionsMalePerfusionQuaternary Ammonium CompoundsRatsRats, Sprague-DawleyRinger's SolutionSodiumSodium-Hydrogen ExchangersTritiumConceptsNet fluid absorptionRat colonic cryptsCl- channel blockerFluid absorptionNeurohumoral stimulationChannel blockersColonic cryptsLumen ClAbsorptive processesInhibitor of NaCl(-) secretionAbstractTextCrypt cellsExchange inhibitorMicroperfusion techniqueFluid secretionL DIDSAmiloride analoguesMammalian colonSecretionAnion exchange inhibitorCryptsSignificant increaseAIMSSecretory process
2000
Cell pH and H+ Secretion by S3 Segment of Mammalian Kidney: Role of H+-ATPase and Cl−
Malnic G, Geibel J. Cell pH and H+ Secretion by S3 Segment of Mammalian Kidney: Role of H+-ATPase and Cl−. The Journal Of Membrane Biology 2000, 178: 115-125. PMID: 11083900, DOI: 10.1007/s002320010019.Peer-Reviewed Original ResearchConceptsProximal tubule cellsChannel blocker NPPBS3 segmentTubule cellsProximal S3 segmentsFree mediumCell pHConfocal microscopyNIH Image programCell pH regulationMicroperfusion techniqueSuperfusionMouse kidneyRabbit kidneyKidneySubcellular vesiclesApical areaCell acidificationMammalian kidneyFluorescence densityNPPBRingerCellsImage programNaCl Ringer
1999
Role of Cl channels in Cl-dependent Na/H exchange
Rajendran V, Geibel J, Binder H. Role of Cl channels in Cl-dependent Na/H exchange. American Journal Of Physiology 1999, 276: g73-g78. PMID: 9886981, DOI: 10.1152/ajpgi.1999.276.1.g73.Peer-Reviewed Original ResearchConceptsNa/H exchangeCl- channel blockerChannel blockersMicroM DIDSNa/H exchange activityCystic fibrosis transmembrane conductance regulatorIntracellular pH recoveryRat distal colonCl- channelsH exchange activityDistal colonCrypt lumenCrypt cellsAcid loadExchange inhibitorApical membranePH recoveryCl(-) dependenceAnion exchange inhibitorCl- channel activityChannel activityBlockersH exchangePolyclonal antibodiesCl- conductance
1997
Intracellular Acidification Induces Cl/HCO3 Exchange Activity in the Basolateral Membrane of β-intercalated Cells of the Rabbit Cortical Collecting Duct
Merot J, Giebisch G, Geibel J. Intracellular Acidification Induces Cl/HCO3 Exchange Activity in the Basolateral Membrane of β-intercalated Cells of the Rabbit Cortical Collecting Duct. The Journal Of Membrane Biology 1997, 159: 253-262. PMID: 9312214, DOI: 10.1007/s002329900288.Peer-Reviewed Original ResearchConceptsBeta-intercalated cellsCortical collecting ductsRabbit cortical collecting ductsHCO3- exchange activityAcid-base transportersProfound decreaseChloride-bicarbonate exchangerCollecting ductsBasolateral additionBasolateral DIDSPH recoveryApical applicationIntracellular pHCell pHDifferent lag periodsBasolateral membraneCellsDuctAcid loading
1995
Chloride-dependent Na-H Exchange A NOVEL MECHANISM OF SODIUM TRANSPORT IN COLONIC CRYPTS*
Rajendran V, Geibel J, Binder H. Chloride-dependent Na-H Exchange A NOVEL MECHANISM OF SODIUM TRANSPORT IN COLONIC CRYPTS*. Journal Of Biological Chemistry 1995, 270: 11051-11054. PMID: 7744735, DOI: 10.1074/jbc.270.19.11051.Peer-Reviewed Original ResearchConceptsNa-H exchangeColonic crypt cellsCrypt cellsAcid loadRat distal colonApical membrane vesiclesNovel transport processRate of intracellularDistal colonMM amilorideSodium transportApical membraneGradient stimulationColonic cryptsAmiloride inhibitionSodium movementNovel mechanismOutward gradientCompelling evidenceCellsSodiumUptakePrior studiesColonRecovery