2014
Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1
Vucic E, Alfadda T, MacGregor GG, Dong K, Wang T, Geibel JP. Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflügers Archiv - European Journal Of Physiology 2014, 467: 1457-1468. PMID: 25127675, DOI: 10.1007/s00424-014-1593-0.Peer-Reviewed Original ResearchConceptsGastric parietal cellsPotassium channelsParietal cellsΒ-subunitKir1.1 channelsWild-type miceSecretagogue-stimulated gastric acid secretionApical poleGastric glandsLeak pathwayPotential therapeutic targetKir1.1Proton secretionRegulatory characteristicsKv7.1Therapeutic targetATPaseCell numberParietal cell numberCellsNormal gastric acid secretionSecretionInhibitorsAcid secretionMiceCalcium-sensing receptor 20 years later
Alfadda TI, Saleh AM, Houillier P, Geibel JP. Calcium-sensing receptor 20 years later. American Journal Of Physiology - Cell Physiology 2014, 307: c221-c231. PMID: 24871857, PMCID: PMC4121584, DOI: 10.1152/ajpcell.00139.2014.Peer-Reviewed Original ResearchConceptsCellular ion transport mechanismsG protein-coupled receptor familyProtein-coupled receptor familyEnvironmental cuesExtracellular environmentOrgan physiologyReceptor familySense changesDifferent tissuesCellular levelCalcium-sensing receptorIon transport mechanismsPhysiologyReceptor physiologyAmino acid concentrationsDisease statesReceptorsSystemic physiologyDiversity of locationsReceptor mutationsDifferent organ systemsImportant roleMembersFamilyHomology
2013
Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR
Collaco AM, Geibel P, Lee BS, Geibel JP, Ameen NA. Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR. American Journal Of Physiology - Cell Physiology 2013, 305: c981-c996. PMID: 23986201, PMCID: PMC4109618, DOI: 10.1152/ajpcell.00067.2013.Peer-Reviewed Original ResearchConceptsV-ATPaseCystic fibrosis transmembrane conductance regulator (CFTR) channelV-ATPase complexV-ATPase functionBrush border membraneProton effluxRat Brunner's glandsIntestinal cellsCAMP/PKACaco-2BBe cellsBorder membraneApical domainCoimmunoprecipitation studiesCFTR distributionVacuolar ATPasesSubapical cytoplasmSpecific subunitsCAMP stimulationProton pumpCAMP treatmentEnterocyte brush border membraneSodium-hydrogen exchangerHydrogen exchangerApical membraneCFTRActivation 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 levelsMetforminThe calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule
Capasso G, Geibel PJ, Damiano S, Jaeger P, Richards WG, Geibel JP. The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule. Kidney International 2013, 84: 277-284. PMID: 23615500, DOI: 10.1038/ki.2013.137.Peer-Reviewed Original ResearchMeSH KeywordsAcid-Base EquilibriumAnimalsCalcimimetic AgentsCalciumHydrogen-Ion ConcentrationIn Vitro TechniquesKidney Tubules, ProximalMaleMiceMice, KnockoutNuclear ProteinsPerfusionPuncturesRatsRats, Sprague-DawleyReceptors, Calcium-SensingReceptors, G-Protein-CoupledSodium-Hydrogen ExchangersTranscription FactorsConceptsProximal tubulesLuminal calcium concentrationFluid reabsorptionAcid secretionKnockout miceCalcium ion concentrationCalcium concentrationRole of CaSRActivation of CaSRCalcium sensing receptorCalcium-sensing receptorMouse proximal tubulesProton secretionSodium-hydrogen exchangerCalcimimetic agentBicarbonate absorptionSensing receptorCaSRFluid absorptionSecretionReabsorptionMiceCalcimimeticsTubulesLuminal membrane
2011
Angiotensin 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 dyesFibrosisPathwayCFTR
2009
AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion
Sidani S, Kopic S, Socrates T, Kirchhoff P, Föller M, Murek M, Capasso A, Geibel JP. AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion. Pflügers Archiv - European Journal Of Physiology 2009, 459: 39. PMID: 19621238, DOI: 10.1007/s00424-009-0698-3.Peer-Reviewed Original ResearchConceptsProtein kinaseAMPK activationSecretagogue-induced acid secretionCellular ATP levelsPresence of AMPKEnergy-dependent transportersImmunofluorescent localizationParietal cellsGastric glandsCellular ATP consumptionGastric parietal cellsCompound CAMPKProton effluxATP consumptionMetabolic stressRate of intracellularATP levelsKinaseAdenosine monophosphateRegulatorATPLarge abundanceCellsActivation
2008
Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins
Wagner CA, Loffing-Cueni D, Yan Q, Schulz N, Fakitsas P, Carrel M, Wang T, Verrey F, Geibel JP, Giebisch G, Hebert SC, Loffing J. Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins. American Journal Of Physiology. Renal Physiology 2008, 294: f1373-f1380. PMID: 18322017, DOI: 10.1152/ajprenal.00613.2007.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsBartter SyndromeCarrier ProteinsCation Transport ProteinsDinoprostoneDisease Models, AnimalEpithelial Sodium ChannelsKidney Tubules, DistalKidney Tubules, ProximalLoop of HenleMiceMice, Mutant StrainsPotassium Channels, Inwardly RectifyingReverse Transcriptase Polymerase Chain ReactionSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Phosphate Cotransporter Proteins, Type IIaSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 1Up-RegulationWaterConceptsThick ascending limbBartter's syndromeBartter-like phenotypeType II Bartter's syndromeWild-type miceAntenatal Bartter syndromeWild-type littermatesROMK null micePlasma aldosteroneMaternal polyhydramniosRenal sodiumVolume depletionRenal tubulopathyMouse modelSemiquantitative immunoblottingProximal tubulesAscending limbKidney homogenatesSyndromeHenle's loopNull miceDCT cellsWater transport proteinsCompensatory mechanismsMice
2006
ΔF508 Mutation Results in Impaired Gastric Acid Secretion*
Sidani SM, Kirchhoff P, Socrates T, Stelter L, Ferreira E, Caputo C, Roberts KE, Bell RL, Egan ME, Geibel JP. ΔF508 Mutation Results in Impaired Gastric Acid Secretion*. Journal Of Biological Chemistry 2006, 282: 6068-6074. PMID: 17178714, DOI: 10.1074/jbc.m608427200.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorATP-binding cassette (ABC) transportersFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorMouse gastric glandsParietal cellsMultifunctional proteinCFTR proteinRegulatory proteinsTransport proteinsCassette transportersConductance regulatorRegulatory roleApical poleSecretagogue-induced acid secretionGland lumenGastric glandsSulfonylurea receptorProteinImpaired gastric acid secretionK-ATPaseCl(-) secretionImmunofluorescent localizationCl- channelsATP-sensitive potassium channelsCalcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction
Geibel J, Sritharan K, Geibel R, Geibel P, Persing JS, Seeger A, Roepke TK, Deichstetter M, Prinz C, Cheng SX, Martin D, Hebert SC. Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9390-9397. PMID: 16760252, PMCID: PMC1475505, DOI: 10.1073/pnas.0602996103.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorCholera toxinFluid secretionNet fluid secretionSecretagogue-induced increasesIntestinal fluid transportCaSR agonistsSecretagogue actionUnique therapyCaSR signalingSecretory actionSecretory diarrheaReceptor activationIntestinal tractEpithelial cellsEnterotoxin STaReceptorsCyclic nucleotidesSecretionExtracellular milieuDiverse cellsToxinActivationCellsDiarrheaThe KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion*
Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP, Lerner DJ, Abbott GW. The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion*. Journal Of Biological Chemistry 2006, 281: 23740-23747. PMID: 16754665, DOI: 10.1074/jbc.m604155200.Peer-Reviewed Original ResearchConceptsAncillary subunitsKCNE gene familyGastric acid secretionPotassium channel alpha subunitFirst genetic evidenceSecretory cellsProton secretionChannel alpha subunitGene familyKCNE familyParietal cell morphologyAcid secretionGenetic evidenceAlpha subunitHuman cardiac arrhythmiasParietal cellsChannel complexSubunitsCell morphologyKCNE2Normal gastrointestinal functionGenesKCNQ1Gene-dose effectCells
2005
The B1-subunit of the H+ ATPase is required for maximal urinary acidification
Finberg KE, Wagner CA, Bailey MA, Păunescu T, Breton S, Brown D, Giebisch G, Geibel JP, Lifton RP. The B1-subunit of the H+ ATPase is required for maximal urinary acidification. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13616-13621. PMID: 16174750, PMCID: PMC1224669, DOI: 10.1073/pnas.0506769102.Peer-Reviewed Original ResearchConceptsMaximal urinary acidificationNormal urinary acidificationMetabolic acidosisUrinary acidificationDistal renal tubular acidosisAcid challengeRenal tubular acidosisAcute intracellular acidificationB1 subunitLumen-negative potentialFurosemide infusionTubular acidosisAlkaline urineDistal nephronGreater severityAcidosisMiceLoss of B1Intracellular acidificationApical expressionUrineDuctFurther decreaseIsoformsPlasma membranel-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells
Busque SM, Kerstetter JE, Geibel JP, Insogna K. l-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. AJP Gastrointestinal And Liver Physiology 2005, 289: g664-g669. PMID: 15961860, DOI: 10.1152/ajpgi.00096.2005.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorAbsence of secretagoguesAcid secretionParietal cellsHistamine-2 receptorSystem L amino acid transportGastric acid secretionWhole stomach preparationDose-dependent increaseIndividual parietal cellsStomach preparationRat gastric glandsHEK-293 cellsCaSRL-amino acidsGastric glandsHormonal stimulationATPase activitySecretionPhysiological concentrationsReceptorsSecretagoguesAcid transportAmino acidsSecretory cells
2004
Nongenomic stimulation of vacuolar H+-ATPases in intercalated renal tubule cells by aldosterone
Winter C, Schulz N, Giebisch G, Geibel JP, Wagner CA. Nongenomic stimulation of vacuolar H+-ATPases in intercalated renal tubule cells by aldosterone. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 2636-2641. PMID: 14983061, PMCID: PMC357002, DOI: 10.1073/pnas.0307321101.Peer-Reviewed Original ResearchConceptsAcid-base homeostasisMineralocorticoid receptorStimulatory effectAldosterone-induced stimulationSystemic acid-base homeostasisDistal tubular acidosisRenal tubule cellsAcid-base statusNongenomic modulationNongenomic stimulationRenal collecting ductsAngiotensin IITransepithelial pH gradientTubular acidosisUrine acidificationAldosteroneATPase activityRenal acidificationHydrogen secretionIntracellular Ca2Complete reabsorptionATPase stainingTubule cellsCollecting ductsNongenomic pathways
2003
Localization and Regulation of the ATP6V0A4 (a4) Vacuolar H+-ATPase Subunit Defective in an Inherited Form of Distal Renal Tubular Acidosis
Stehberger PA, Schulz N, Finberg KE, Karet FE, Giebisch G, Lifton RP, Geibel JP, Wagner CA. Localization and Regulation of the ATP6V0A4 (a4) Vacuolar H+-ATPase Subunit Defective in an Inherited Form of Distal Renal Tubular Acidosis. Journal Of The American Society Of Nephrology 2003, 14: 3027-3038. PMID: 14638902, DOI: 10.1097/01.asn.0000099375.74789.ab.Peer-Reviewed Original ResearchConceptsDistal renal tubular acidosisRenal tubular acidosisLoop of HenleProximal tubulesTubular acidosisMouse kidneyA4 expressionDistal tubulesDistal convoluted tubuleProtein expression levelsElectrolyte intakeA4 proteinConvoluted tubulesMouse nephron segmentsNephron segmentsApical stainingWestern blottingAcidosisProtein expressionKidneyATPase activityDistal portionHenleExpression levelsTubulesMolecular cloning and characterization of Atp6v1b1, the murine vacuolar H+-ATPase B1-subunit
Finberg KE, Wagner CA, Stehberger PA, Geibel JP, Lifton RP. Molecular cloning and characterization of Atp6v1b1, the murine vacuolar H+-ATPase B1-subunit. Gene 2003, 318: 25-34. PMID: 14585495, DOI: 10.1016/s0378-1119(03)00790-x.Peer-Reviewed Original ResearchMeSH Keywords5' Flanking RegionAmino Acid SequenceAnimalsAntibody SpecificityBase SequenceCloning, MolecularDNADNA, ComplementaryEpididymisGene Expression Regulation, EnzymologicHumansImmune SeraImmunohistochemistryIsoenzymesKidneyMaleMiceMice, Inbred StrainsMolecular Sequence DataPhylogenyProtein SubunitsRNA, MessengerSequence AlignmentSequence Analysis, DNASequence Homology, Amino AcidSequence Homology, Nucleic AcidVacuolar Proton-Translocating ATPasesConceptsDistal renal tubular acidosisRenal tubular acidosisMouse renal cortexProton-translocating ATPasesTubular acidosisRenal cortexSubset of tissuesAnimal modelsATP6V1B1Major organsGenomic organizationGenomic lociMouse kidneyProtein levelsMolecular cloningAcid proteinPlasma membraneMurine orthologIntracellular organellesB1 isoformKidneyNorthern blottingA rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse
Wagner CA, Lükewille U, Valles P, Breton S, Brown D, Giebisch GH, Geibel JP. A rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse. Pflügers Archiv - European Journal Of Physiology 2003, 446: 623-632. PMID: 12748863, DOI: 10.1007/s00424-003-1082-3.Peer-Reviewed Original ResearchConceptsProximal tubulesTubule fragmentsMouse kidneyKidney tubule fragmentsCollagenase digestion techniqueMouse proximal tubulesUnits/minTrypan blue exclusionKidney functionInner stripeOuter medullaIntercalated cellsIndependent intracellularBlue exclusionTrypan blueTubulesKidneyMicePH-sensitive dyeLight microscopyDuctAnimalsFurther characterizationATPase activityFunctional characteristics
2002
Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status
Wagner CA, Finberg KE, Stehberger PA, Lifton RP, Giebisch GH, Aronson PS, Geibel JP. Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status. Kidney International 2002, 62: 2109-2117. PMID: 12427135, DOI: 10.1046/j.1523-1755.2002.00671.x.Peer-Reviewed Original ResearchConceptsPendrin-positive cellsAcid-base statusPositive cellsBicarbonate secretionMouse kidneyAcid-base transportKnockout mouse modelProtein expression levelsMetabolic alkalosisDeficient dietExchanger pendrinPendrin expressionMouse modelSensorineural deafnessThyroid glandBicarbonate loadPendred syndromeWestern blottingApical membraneInner earPendrin proteinControl levelsKidneyPendrinProtein levels
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