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
2002
Role of c-SRC and ERK in acid-induced activation of NHE3
Tsuganezawa H, Sato S, Yamaji Y, Preisig PA, Moe OW, Alpern RJ. Role of c-SRC and ERK in acid-induced activation of NHE3. Kidney International 2002, 62: 41-50. PMID: 12081562, DOI: 10.1046/j.1523-1755.2002.00418.x.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAmmonium ChlorideAnimalsCells, CulturedCSK Tyrosine-Protein KinaseEnzyme ActivationJNK Mitogen-Activated Protein KinasesMaleMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesPhosphorylationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleySodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSrc-Family KinasesConceptsOKP cellsAcid-induced activationNHE3 activityERK/c-fosC-fos expressionC-Fos activationCytoplasmic pH (pHi) recoveryC-SrcRenal proximal tubulesAcid incubationActivation of NHE3Renal epithelial cellsCultured renal epithelial cellsProximal tubulesChronic acidosisInhibition of MEKNHE3 activationInhibited activationNormal levelsAcid loadImmune complex kinase assayERK kinaseAcidosisPH recoveryEpithelial cellsGlucagon 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
1997
The clinical spectrum of chronic metabolic acidosis: Homeostatic mechanisms produce significant morbidity
Alpern R, Sakhaee K. The clinical spectrum of chronic metabolic acidosis: Homeostatic mechanisms produce significant morbidity. American Journal Of Kidney Diseases 1997, 29: 291-302. PMID: 9016905, DOI: 10.1016/s0272-6386(97)90045-7.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisHomeostatic responseSerum HCO3Acid loadBody's homeostatic responseHomeostatic mechanismsMuscle protein breakdownNormal homeostatic mechanismsSignificant morbidityClinical spectrumMeat ingestionBone demineralizationRenal growthClinical conditionsPathologic processesPathologic consequencesAcidosisProtein breakdownBloodResponseMorbidityPatientsNephrolithiasisIngestion
1993
Glucocorticoids stimulate Na+/H+ antiporter in OKP cells
Baum M, Cano A, Alpern RJ. Glucocorticoids stimulate Na+/H+ antiporter in OKP cells. American Journal Of Physiology 1993, 264: f1027-f1031. PMID: 8391752, DOI: 10.1152/ajprenal.1993.264.6.f1027.Peer-Reviewed Original ResearchConceptsOKP cellsProximal tubule acidificationEffect of dexamethasoneAntiporter activityTime-dependent stimulationM aldosteroneHemodynamic changesTubule acidificationSystemic administrationDependent pH recoveryDexamethasoneM dexamethasoneAcid loadStimulatory effectGlucocorticoidsPH recoveryStimulationPH-sensitive dyePresent studyMaximal velocityCellsDirect effectAldosteronePrevious studiesActivity
1992
Citraturic Response to Oral Citric Acid Load
Sakhaee K, Alpern R, Poindexter J, Pak C. Citraturic Response to Oral Citric Acid Load. Journal Of Urology 1992, 147: 975-976. PMID: 1552616, DOI: 10.1016/s0022-5347(17)37437-2.Peer-Reviewed Original ResearchConceptsAcid loadCitraturic responseUrinary citrateCarbon dioxide pressureSingle oral loadUrinary citrate excretionSingle oral doseSerum citrate concentrationAcid-base balanceCitraturic effectsOral loadVenous pHOral doseSerum electrolytesUrinary pHCitrate excretionNormal subjectsAlkali loadPotassium citrateSignificant differencesHoursTotal carbon dioxideCitrateExcretionCitrate concentration
1991
Inhibition of Na(+)-independent H+ pump by Na(+)-induced changes in cell Ca2+.
Hays SR, Alpern RJ. Inhibition of Na(+)-independent H+ pump by Na(+)-induced changes in cell Ca2+. The Journal Of General Physiology 1991, 98: 791-813. PMID: 1660062, PMCID: PMC2229082, DOI: 10.1085/jgp.98.4.791.Peer-Reviewed Original ResearchConceptsCell pH recoveryCell Ca2PH recoveryAcid loadPump activityRenal outer medullaryDelayed activationCell acidificationRapid cell acidificationUnits/minApical membraneCell pHSustained elevationFura-2Outer medullaryExtracellular Ca2Inner stripeIntracellular Ca2Steady-state cell pHSustained increaseDimethyl-BAPTAInitial suppressionSpike increasePhysiologic ratesMicrofilament-disrupting agent
1990
Apical and basolateral membrane H+ extrusion mechanisms in inner stripe of rabbit outer medullary collecting duct
Hays SR, Alpern RJ. Apical and basolateral membrane H+ extrusion mechanisms in inner stripe of rabbit outer medullary collecting duct. American Journal Of Physiology 1990, 259: f628-f635. PMID: 2171359, DOI: 10.1152/ajprenal.1990.259.4.f628.Peer-Reviewed Original ResearchConceptsUnits/minPHi recoveryInner stripeAcid loadInitial control levelsSCH 28080Luminal Sch-28080ATPase inhibitorBasolateral membraneTriphasic responseExtrusion mechanismSlow alkalinizationRate of alkalinizationControl levelsCell acidificationRabbitsInhibitorsDuctTotal absenceInitial rateAlkalinizationN-ethylmaleimideRecoveryMin