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 acidRhoA 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 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
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 cells
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
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 ResearchMeSH KeywordsAcidosis, Renal TubularAnimalsCytoplasmHydrogen-Ion ConcentrationIonophoresKidney Tubules, ProximalNigericinOpossumsSodium-Hydrogen Exchanger 3Sodium-Hydrogen Exchangers
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 ResearchGlucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3)
Ambühl P, Yang X, Peng Y, Preisig P, Moe O, Alpern R. Glucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3). Journal Of Clinical Investigation 1999, 103: 429-435. PMID: 9927505, PMCID: PMC407891, DOI: 10.1172/jci2913.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCell LineGlucocorticoidsHydrogen-Ion ConcentrationSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsNHE3 protein abundanceM hydrocortisoneNHE3 activityAcid incubationNHE3 mRNA abundanceTrafficking of NHE3Absence of hydrocortisoneOpossum kidney cellsExogenous glucocorticoidsExchanger 3 (NHE3) activityHydrocortisoneProtein abundanceGlucocorticoidsProtein synthesisExchanger 3Kidney cellsTwofold increaseMRNA abundanceApical membrane
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 ResearchMeSH KeywordsAmilorideAnimalsCell LineCulture MediaGlucoseHypertonic SolutionsKidneyMannitolOpossumsOsmolar ConcentrationRaffinoseSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersUreaConceptsNa/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
Chronic 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
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 ResearchMeSH KeywordsAnimalsBicarbonatesGene ExpressionGenes, srcHumansKidney Tubules, ProximalSignal TransductionSodium-Hydrogen ExchangersTime FactorsConceptsNa/H antiporterChronic regulationH secretionProximal tubulesH antiporterNaCl absorptionProximal tubular acidificationMajor siteNa/K pumpCitrate reabsorptionBasolateral membraneTubular acidificationAcute regulationLuminal membraneK pumpExcretionReabsorptionSecretionPivotal roleVacuolar H-ATPaseH-ATPaseTubulesOverexpression 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 AcetateTransfection
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 acidificationChronic regulation of the Na/H antiporter.
Alpern RJ, Yamaji Y, Cano A, Horie S, Miller RT, Moe OW, Preisig PA. Chronic regulation of the Na/H antiporter. Translational Research 1993, 122: 137-40. PMID: 8393472.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCells, CulturedGene Expression RegulationHydrogenHydrogen-Ion ConcentrationKidneyProtein KinasesSodiumSodium-Hydrogen ExchangersConceptsNa/H antiporter activityNa/H antiporterChronic regulationH antiporterAcute inhibitory effectRabbit proximal tubule cellsAcid-induced increaseProximal tubule cellsOpossum kidney cellsMRNA abundanceProtein kinase AChronic decreaseAntiporter activityChronic studiesChronic activationTubule cellsImmediate early genesIntact animalsKinase AInhibitory effectProtein synthesisNonrenal cellsPrimary culturesC-fosExtracellular fluid