2018
Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways
Zacchia M, Tian X, Zona E, Alpern RJ, Preisig PA. Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways. Journal Of The American Society Of Nephrology 2018, 29: 1720-1730. PMID: 29678998, PMCID: PMC6054333, DOI: 10.1681/asn.2017121268.Peer-Reviewed Original ResearchMeSH KeywordsAcidsAmmonium ChlorideAnimalsCells, CulturedCitric AcidCSK Tyrosine-Protein KinaseDicarboxylic Acid TransportersEndothelin-1Epithelial CellsFocal Adhesion Kinase 2Kidney Tubules, ProximalMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3OpossumsOrganic Anion Transporters, Sodium-DependentPhosphorylationProto-Oncogene Proteins c-rafReceptor, Endothelin BRibosomal Protein S6 Kinases, 90-kDaSrc-Family KinasesTransfectionConceptsET-1/ETEndothelin-1Proximal tubulesCultured opossum kidney cellsAcid stimulationInhibition of Pyk2ET-1 stimulationRenal proximal tubulesNaDC-1Opossum kidney cellsCl loadingC-SrcPhosphorylation of Raf1Urine citratePyk2 knockdownEnd pointAcid loadApical NaERK1/2 pathwayStimulationMiceKidney cellsKidneyPyk2ERK1/2
2010
Acid regulation of NaDC-1 requires a functional endothelin B receptor
Liu L, Zacchia M, Tian X, Wan L, Sakamoto A, Yanagisawa M, Alpern RJ, Preisig PA. Acid regulation of NaDC-1 requires a functional endothelin B receptor. Kidney International 2010, 78: 895-904. PMID: 20703215, DOI: 10.1038/ki.2010.264.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAnimalsBiological TransportCell LineDicarboxylic Acid TransportersDisease Models, AnimalEndothelin B Receptor AntagonistsEndothelin-1Hydrogen-Ion ConcentrationKidneyMiceMice, KnockoutMicrovilliOligopeptidesOpossumsOrganic Anion Transporters, Sodium-DependentPiperidinesProtein Structure, TertiaryReceptor, Endothelin AReceptor, Endothelin BRecombinant Fusion ProteinsSignal TransductionSymportersTime FactorsTransfectionConceptsEndothelin-1Endothelin-B receptor antagonistFunctional endothelin B receptorsStimulatory effectAcid-stimulatory effectET-1 effectsB receptor antagonistNHE3 activityEndothelin B receptorWild-type miceET-1 stimulationMajor physiological stimulusNaDC-1Acid ingestionReceptor antagonistCitrate reabsorptionReceptor expressionCitrate excretionOpossum kidneyAcid loadB receptorAcid feedingPhysiological stimuliStimulationMice
2007
RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3
Yang X, Huang HC, Yin H, Alpern RJ, Preisig PA. RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3. American Journal Of Physiology. Renal Physiology 2007, 293: f1054-f1064. PMID: 17686951, DOI: 10.1152/ajprenal.00295.2007.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnimalsBenzoquinonesCell LineEnzyme InhibitorsExocytosisFocal Adhesion Kinase 1Hydrochloric AcidHydrogen-Ion ConcentrationLactams, MacrocyclicOpossumsPaxillinPhosphorylationProtein-Tyrosine KinasesPyridinesRhoA GTP-Binding ProteinRifabutinSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersStress FibersTyrosineConceptsStress fiber formationTyrosine phosphorylationFiber formationFocal adhesion proteinsApical membraneRho-kinaseNHE3 activityExocytic traffickingActivation of NHE3Exocytic processFocal adhesionsNHE3 exocytosisAdhesion proteinsStress fibersProtein abundancePaxillinPhosphorylationMicrofilament structureAntiporter activityKinaseRho-kinase inhibitorKinase inhibitorsTraffickingAbundanceNHE3 activation
2004
Pyk2 activation is integral to acid stimulation of sodium/hydrogen exchanger 3
Li S, Sato S, Yang X, Preisig PA, Alpern RJ. Pyk2 activation is integral to acid stimulation of sodium/hydrogen exchanger 3. Journal Of Clinical Investigation 2004, 114: 1782-1789. PMID: 15599403, PMCID: PMC535061, DOI: 10.1172/jci18046.Peer-Reviewed Original ResearchAcidsAdenosine TriphosphateADP-Ribosylation FactorsAnimalsCell LineCell-Free SystemFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGenes, DominantGTPase-Activating ProteinsHydrogen-Ion ConcentrationImmunoblottingImmunoprecipitationKidney TubulesMutationOpossumsPhosphorylationProtein BindingProtein-Tyrosine KinasesRatsRats, Sprague-DawleyRNARNA, Small InterferingSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersTime FactorsTransfectionA consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1
Laghmani K, Sakamoto A, Yanagisawa M, Preisig PA, Alpern RJ. A consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1. American Journal Of Physiology. Renal Physiology 2004, 288: f732-f739. PMID: 15598844, DOI: 10.1152/ajprenal.00300.2004.Peer-Reviewed Original ResearchConceptsEndothelin-1Second intracellular loopET-1 stimulationNHE3 activityIntracellular loopEndothelin-A receptorAdenylyl cyclase inhibitionET-1 regulationProximal tubule apical membraneET receptorsCyclase inhibitionOKP cellsNHE3 activationOpossum kidneyExchanger 3ReceptorsStimulationProtein tyrosine phosphorylationReceptor chimerasPresent studyCellsAdditional mechanismTyrosine phosphorylationApical membraneSimilar patternOKP cells express the Na-dicarboxylate cotransporter NaDC-1
Aruga S, Pajor AM, Nakamura K, Liu L, Moe OW, Preisig PA, Alpern RJ. OKP cells express the Na-dicarboxylate cotransporter NaDC-1. American Journal Of Physiology - Cell Physiology 2004, 287: c64-c72. PMID: 14973148, DOI: 10.1152/ajpcell.00061.2003.Peer-Reviewed Original ResearchConceptsCitrate reabsorptionOKP cellsProximal tubulesDependent citrate uptakeOpossum kidney cell lineUrinary citrate concentrationChronic metabolic acidosisRate of reabsorptionRenal proximal tubulesMetabolic acidosisStone formationKidney stonesKidney cell lineCotransporter 1ReabsorptionCell linesCitrate transportMRNA abundanceXenopus oocytesAcid regulationTubulesNaDC-1Citrate uptakeSuccinate transportHypocitraturia
2002
Glucagon Acutely Inhibits but Chronically Activates Na+/H+ Antiporter 3 Activity in OKP Cells
Amemiya M, Kusano E, Muto S, Tabei K, Ando Y, Alpern RJ, Asano Y. Glucagon Acutely Inhibits but Chronically Activates Na+/H+ Antiporter 3 Activity in OKP Cells. Experimental Nephrology 2002, 10: 26-33. PMID: 11803202, DOI: 10.1159/000049895.Peer-Reviewed Original ResearchConceptsNHE3 protein abundanceOKP cellsNHE3 activityCell pH recoveryRat renal proximal tubulesDibutyryl cAMPThick ascending limbRenal proximal tubulesWestern blot analysisM dibutyryl-cAMPChronic activationPKA-dependent pathwayProximal tubulesAscending limbGlucagonSurface membraneAcid loadNHE3 mRNAProtein abundancePH recoveryExchanger 3Independent mechanismsSignificant increaseBlot analysisP cells
2001
ETB receptor activation causes exocytic insertion of NHE3 in OKP cells
Peng Y, Amemiya M, Yang X, Fan L, Moe O, Yin H, Preisig P, Yanagisawa M, Alpern R. ETB receptor activation causes exocytic insertion of NHE3 in OKP cells. American Journal Of Physiology. Renal Physiology 2001, 280: f34-f42. PMID: 11133512, DOI: 10.1152/ajprenal.2001.280.1.f34.Peer-Reviewed Original ResearchConceptsEndothelin-1Sodium/hydrogen exchanger 3ET-1-induced increaseTotal cellular NHE3NHE3 activityNET traffickingTwo- to threefold increaseApical membrane NHE3OKP cellsMaximal effectReceptor activationClone PApical NHE3Exchanger 3NHE3Exocytic insertionThreefold increaseApical membraneCytochalasin D
2000
Acid incubation causes exocytic insertion of NHE3 in OKP cells
Yang X, Amemiya M, Peng Y, Moe O, Preisig P, Alpern R. Acid incubation causes exocytic insertion of NHE3 in OKP cells. American Journal Of Physiology - Cell Physiology 2000, 279: c410-c419. PMID: 10913008, DOI: 10.1152/ajpcell.2000.279.2.c410.Peer-Reviewed Original Research
1999
Incubation of OKP cells in low-K+ media increases NHE3 activity after early decrease in intracellular pH
Amemiya M, Tabei K, Kusano E, Asano Y, Alpern R. Incubation of OKP cells in low-K+ media increases NHE3 activity after early decrease in intracellular pH. American Journal Of Physiology 1999, 276: c711-c716. PMID: 10069999, DOI: 10.1152/ajpcell.1999.276.3.c711.Peer-Reviewed Original ResearchConceptsOKP cellsEarly decreaseNHE3 activityNHE3 protein abundanceTyrosine kinase inhibitorsProximal tubule apical membraneChronic hypokalemiaTyrosine kinase pathwayIntracellular acidosisNHE3 mRNAKinase inhibitorsControl levelsNHE3Herbimycin AKinase pathwayControl mediumPresent studySodium propionateIntracellularCellsAntiporter activityApical membraneHypokalemiaIncubationProtein abundance
1998
Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells
Tsuganezawa H, Preisig P, Alpern R. Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells. Kidney International 1998, 54: 394-398. PMID: 9690205, DOI: 10.1046/j.1523-1755.1998.00029.x.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityAngiotensin IIOKP cellsInhibits angiotensin IIVascular smooth muscleTyrosine kinase inhibitorsC-SrcHerbimycin AAntiporter activityNa/H antiporterActivation of NHE3Smooth muscleProximal tubulesPotent stimulatorNHE3 activationRegulation of NHE3Key mediatorKinase inhibitorsClonal cell linesNHE3 activityAntiporter activationCyclic AMPCell linesNHE3AcidosisChronic hyperosmolality increases NHE3 activity in OKP cells.
Ambühl P, Amemiya M, Preisig PA, Moe OW, Alpern RJ. Chronic hyperosmolality increases NHE3 activity in OKP cells. Journal Of Clinical Investigation 1998, 101: 170-177. PMID: 9421479, PMCID: PMC508553, DOI: 10.1172/jci62.Peer-Reviewed Original ResearchConceptsNa/H exchanger 3Na/H antiporter activityDiabetes mellitusNHE3 mRNA abundanceNHE3 protein abundanceAntiporter activityChronic hypertonicityGlomerular hyperfiltrationDiabetic nephropathyNa/H antiporterChronic hyperosmolalityOKP cellsExchanger 3MOsm/NHE3 activityRelevant increaseMellitusSignificant increaseChronicH antiporterExtracellular glucoseHypertonic incubationMRNA abundanceHypertonicitySmall increase
1996
Glucocorticoids regulate NHE-3 transcription in OKP cells
Baum M, Amemiya M, Dwarakanath V, Alpern RJ, Moe OW. Glucocorticoids regulate NHE-3 transcription in OKP cells. American Journal Of Physiology 1996, 270: f164-f169. PMID: 8769835, DOI: 10.1152/ajprenal.1996.270.1.f164.Peer-Reviewed Original ResearchConceptsNHE-3 mRNA abundanceGlucocorticoid-mediated increaseOKP cellsDexamethasone-treated cellsNHE-3 mRNAMRNA abundanceTwo- to threefold increaseAntiporter activitySynthetic glucocorticoidProximal tubulesApical proton secretionM dexamethasoneDexamethasoneNHE-3GlucocorticoidsTime courseProton secretionThreefold increasePresent studyCellsGene transcriptionMRNASecretionActivity
1995
Overexpression of csk inhibits acid-induced activation of NHE-3.
Yamaji Y, Amemiya M, Cano A, Preisig PA, Miller RT, Moe OW, Alpern RJ. Overexpression of csk inhibits acid-induced activation of NHE-3. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 6274-6278. PMID: 7541536, PMCID: PMC41500, DOI: 10.1073/pnas.92.14.6274.Peer-Reviewed Original Research1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAnimalsBenzoquinonesCell LineChickensCSK Tyrosine-Protein KinaseGene ExpressionGene Expression RegulationHydrogen-Ion ConcentrationIsoquinolinesKidneyKineticsLactams, MacrocyclicOpossumsPiperazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins pp60(c-src)QuinonesRecombinant ProteinsRifabutinSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSrc-Family KinasesTetradecanoylphorbol AcetateTransfectionAcid incubation increases NHE-3 mRNA abundance in OKP cells
Amemiya M, Yamaji Y, Cano A, Moe OW, Alpern RJ. Acid incubation increases NHE-3 mRNA abundance in OKP cells. American Journal Of Physiology 1995, 269: c126-c133. PMID: 7631739, DOI: 10.1152/ajpcell.1995.269.1.c126.Peer-Reviewed Original Research
1994
Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells
Cano A, Miller RT, Alpern RJ, Preisig PA. Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells. American Journal Of Physiology 1994, 266: c1603-c1608. PMID: 8023891, DOI: 10.1152/ajpcell.1994.266.6.c1603.Peer-Reviewed Original ResearchConceptsPertussis toxin-sensitive G proteinToxin-sensitive G proteinNa-H antiporter activityAngiotensin IINa-H antiporterOKP cellsAngiotensin II concentrationAngiotensin II receptorsAbsence of IBMXAngiotensin II stimulationG proteinsCyclic monophosphateProximal tubule apical membraneOpossum kidney cellsConcentration-dependent mannerCAMP-independent mechanismM losartanAcute treatmentAT1 receptorII stimulationPertussis toxinII receptorsProximal tubulesCAMP productionStimulatory effect
1993
Cyclic adenosine monophosphate acutely inhibits and chronically stimulates Na/H antiporter in OKP cells.
Cano A, Preisig P, Alpern RJ. Cyclic adenosine monophosphate acutely inhibits and chronically stimulates Na/H antiporter in OKP cells. Journal Of Clinical Investigation 1993, 92: 1632-1638. PMID: 7691881, PMCID: PMC288321, DOI: 10.1172/jci116748.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityRenal Na excretionNa excretionNa/H antiporterOKP cellsH antiporterAntiporter activityAddition of forskolinParathyroid hormoneAngiotensin IIAcute effectsChronic increaseChronic activationCyclic adenosine monophosphateChronic effectsChronic applicationNonspecific effectsPersistent activationPersistent increaseAlpha-adrenergic catecholaminesCell cAMPEndogenous generationAdenosine monophosphateH exposureCell acidification