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
The acid-activated signaling pathway: Starting with Pyk2 and ending with increased NHE3 activity
Preisig PA. The acid-activated signaling pathway: Starting with Pyk2 and ending with increased NHE3 activity. Kidney International 2007, 72: 1324-1329. PMID: 17882150, DOI: 10.1038/sj.ki.5002543.Peer-Reviewed Original ResearchConceptsTypical Western dietSystemic acid-base balanceMultiple nephron segmentsProximal tubule cellsAcid-base balanceNa/H antiporterWestern dietBicarbonate reclamationProximal tubulesTubule cellsNephron segmentsAcid loadAmmonium secretionLuminal protonsNHE3 activityH antiporterSecretionNHE3Titratable acid
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 patternAn autocrine role for endothelin-1 in the regulation of proximal tubule NHE3
Licht C, Laghmani K, Yanagisawa M, Preisig PA, Alpern RJ. An autocrine role for endothelin-1 in the regulation of proximal tubule NHE3. Kidney International 2004, 65: 1320-1326. PMID: 15086471, DOI: 10.1111/j.1523-1755.2004.00506.x.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisReverse transcription-polymerase chain reactionProximal tubulesKidney cortexCompetitive reverse transcription-polymerase chain reactionProximal tubule NHE3NHE3 activityPreproET-1 expressionEndothelin B receptorEndothelin-1 expressionET-1 expressionPreproET-1 mRNA abundancePreproET-1 mRNA expressionTranscription-polymerase chain reactionProximal tubule cellsRenal proximal tubulesMRNA abundanceEndothelin-1Control ratsAbdominal aortaAutocrine roleAcidosisTubule cellsAutocrine regulationDietary acid, endothelins, and sleep.
Alpern RJ, Preisig PA. Dietary acid, endothelins, and sleep. Transactions Of The American Clinical And Climatological Association 2004, 115: 385-93; discussion 393-4. PMID: 17060981, PMCID: PMC2263788.Peer-Reviewed Original ResearchConceptsTrafficking of NHE3Proximal tubule cell lineNHE3 activityTubule cell lineSecond intracellular loopEndothelin expressionDietary acidNHE3 abundanceActivation of NHE3OKP cellsProximal tubulesNHE3 mRNAApical membraneHomeostatic responseProtein expressionC-fosReceptor specificityIntracellular loopReceptorsEndothelinCell linesC-JunNHE3C-SrcAcid signaling
2001
Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis
Laghmani K, Preisig P, Moe O, Yanagisawa M, Alpern R. Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis. Journal Of Clinical Investigation 2001, 107: 1563-1569. PMID: 11413164, PMCID: PMC200190, DOI: 10.1172/jci11234.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAmmoniaAnimalsBicarbonatesChronic DiseaseCitric AcidCulture TechniquesEndothelin-1EndothelinsKidney Tubules, ProximalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicProtein PrecursorsReceptor, Endothelin BReceptors, EndothelinRNA, MessengerSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsTg/tgAcid ingestionTitratable acid excretionMetabolic acidosisNHE3 activityAcid excretionReceptor-deficient miceEndothelin B receptorET-1 expressionChronic metabolic acidosisProximal tubule suspensionsAmmonium excretionM endothelinNa/H antiporterC57BL/6 miceApical membrane NHE3Renal epithelial cellsCultured renal epithelial cellsEndothelin-1/Tubule suspensionsMRNA expressionControl dietMiceExcretionEpithelial cellsETB 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
1999
ETB receptor activation leads to activation and phosphorylation of NHE3
Peng Y, Moe OW, Chu T, Preisig PA, Yanagisawa M, Alpern RJ. ETB receptor activation leads to activation and phosphorylation of NHE3. American Journal Of Physiology 1999, 276: c938-c945. PMID: 10199826, DOI: 10.1152/ajpcell.1999.276.4.c938.Peer-Reviewed Original Research