2017
Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD
Bushinsky DA, Hostetter T, Klaerner G, Stasiv Y, Lockey C, McNulty S, Lee A, Parsell D, Mathur V, Li E, Buysse J, Alpern R. Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD. Clinical Journal Of The American Society Of Nephrology 2017, 13: 26-35. PMID: 29102959, PMCID: PMC5753317, DOI: 10.2215/cjn.07300717.Peer-Reviewed Original ResearchConceptsSerum bicarbonateEnd of treatmentMetabolic acidosisTreatment groupsBaseline serum bicarbonateMean baseline eGFRMEq/LSignificant adverse effectsBaseline eGFRGastrointestinal eventsAdverse eventsFirst doseControlled TrialsHeart failurePatientsCKDBaseline levelsMean increaseAbstractTextUnit studiesAcidosisAdverse effectsPlaceboTreatmentDays
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
2004
A 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
Renal citrate metabolism and urinary citrate excretion in the infant rat
Melnick J, Preisig P, Alpern R, Baum M. Renal citrate metabolism and urinary citrate excretion in the infant rat. Kidney International 2000, 57: 891-897. PMID: 10720942, PMCID: PMC4089854, DOI: 10.1046/j.1523-1755.2000.057003891.x.Peer-Reviewed Original ResearchConceptsUrinary citrate excretionHigher urinary citrateCitrate excretionInfant ratsAdult ratsUrinary citrateRenal citrate metabolismMitochondrial aconitase activityCreatinine ratioCitrate metabolismRenal excretionSame prevalenceRenal stonesTwofold higher concentrationLower plasmaATP citrate lyase activityProximal tubulesHigher plasmaMetabolic cagesRat kidneyRatsAdult levelsInfantsMaturational differencesExcretion
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
1997
Metabolic alkalosis.
Palmer BF, Alpern RJ. Metabolic alkalosis. Journal Of The American Society Of Nephrology 1997, 8: 1462-9. PMID: 9294840, DOI: 10.1681/asn.v891462.Peer-Reviewed Original ResearchThe 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 breakdownBloodResponseMorbidityPatientsNephrolithiasisIngestionDoes hyperphosphaturla underlle hypercalciuria?
Alpern R, Sakhaee K. Does hyperphosphaturla underlle hypercalciuria? The Lancet 1997, 349: 518-519. PMID: 9048785, DOI: 10.1016/s0140-6736(97)80080-3.Peer-Reviewed Original Research
1996
Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.
Melnick JZ, Srere PA, Elshourbagy NA, Moe OW, Preisig PA, Alpern RJ. Adenosine triphosphate citrate lyase mediates hypocitraturia in rats. Journal Of Clinical Investigation 1996, 98: 2381-2387. PMID: 8941657, PMCID: PMC507690, DOI: 10.1172/jci119051.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisATP citrate lyase activityATP-citrate lyaseCitrate lyase activityCitrate lyaseHypocitraturiaAcid dietAcidosisCitrate metabolismProtein abundanceRatsMRNA abundanceLyase activityMetabolismPresent studySignificant changesCitrate uptakeInhibitionHypercitraturiaHypokalemiaCytosolic enzymeCompetitive inhibitorActivityImportant roleChronic metabolic acidosis increases NHE3 protein abundance in rat kidney
Ambuhl P, Amemiya M, Danczkay M, Lotscher M, Kaissling B, Moe OW, Preisig PA, Alpern RJ. Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney. American Journal Of Physiology 1996, 271: f917-f925. PMID: 8898023, DOI: 10.1152/ajprenal.1996.271.4.f917.Peer-Reviewed Original ResearchConceptsNHE3 protein abundanceChronic metabolic acidosisNHE3 mRNA abundanceMetabolic acidosisThick ascending limbProximal tubulesAscending limbNa/H antiporter activityAcidosis-induced increaseMRNA abundanceNa/H antiporterNHE3 abundanceProtein abundanceAcidosisRat kidneyWestern blotS2 segmentsH antiporterRatsNHE3 isoformPresent studyLimbTubules
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 ResearchInvolvement of pRB family in TGF beta-dependent epithelial cell hypertrophy.
Franch HA, Shay JW, Alpern RJ, Preisig PA. Involvement of pRB family in TGF beta-dependent epithelial cell hypertrophy. Journal Of Cell Biology 1995, 129: 245-254. PMID: 7698989, PMCID: PMC2120382, DOI: 10.1083/jcb.129.1.245.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Polyomavirus TransformingBlotting, NorthernCell CycleCell DivisionCell LineCells, CulturedEpidermal Growth FactorEpithelial CellsEpitheliumGene ExpressionHumansHypertrophyKidneyKidney TubulesKineticsOncogene Proteins, ViralPapillomavirus E7 ProteinsPhosphorylationProto-Oncogene Proteins c-fosRabbitsRatsRecombinant ProteinsRepressor ProteinsRetinoblastoma ProteinRNA, MessengerTransfectionTransforming Growth Factor betaTumor Suppressor Protein p53ConceptsEpithelial cell hypertrophyNRK-52E cellsCell hypertrophyHPV16 E6TGF betaSV40 large T antigenC-fos mRNA abundanceGrowth factor beta 1SV40 large T antigen expressionLarge T antigenLarge T antigen expressionMechanisms of hypertrophyRenal cell hypertrophyRabbit proximal tubuleActive pRbT-antigen expressionRenal functionT antigenRenal hypertrophyAntigen expressionEpidermal growth factorEGF-induced increaseProximal tubulesHypertrophyHPV16 E7
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