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
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 FactorsTransfection
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
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
Chronic regulation of the proximal tubular Na/H antiporter: From HCO3 to SRC
Alpern R, Moe O, Preisig P. Chronic regulation of the proximal tubular Na/H antiporter: From HCO3 to SRC. Kidney International 1995, 48: 1386-1396. PMID: 8544394, DOI: 10.1038/ki.1995.427.Peer-Reviewed Original ResearchConceptsNa/H antiporterChronic regulationH secretionProximal tubulesH antiporterNaCl absorptionProximal tubular acidificationMajor siteNa/K pumpCitrate reabsorptionBasolateral membraneTubular acidificationAcute regulationLuminal membraneK pumpExcretionReabsorptionSecretionPivotal roleVacuolar H-ATPaseH-ATPaseTubules
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
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