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 cells
1998
Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia
Melnick J, Preisig P, Haynes S, Pak C, Sakhaee K, Alpern R. Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia. Kidney International 1998, 54: 1670-1674. PMID: 9844143, DOI: 10.1046/j.1523-1755.1998.00150.x.Peer-Reviewed Original ResearchConceptsUrinary citrate excretionCitrate excretionUrinary citrateMetabolic acidosisATP-citrate lyaseEffects of enalaprilRenal citrate metabolismUrine citrate concentrationRenal cortical tissueChronic metabolic acidosisProximal tubular cellsPlasma pHNa/H antiporterAngiotensin IIIntracellular acidosisEnalaprilTubular cellsCitrate lyaseHypokalemiaEnzyme inhibitorsATP citrate lyase activityAcidosisCortical tissueRatsCitrate metabolismDominant 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
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 ResearchConceptsNa/H antiporterChronic regulationH secretionProximal tubulesH antiporterNaCl absorptionProximal tubular acidificationMajor siteNa/K pumpCitrate reabsorptionBasolateral membraneTubular acidificationAcute regulationLuminal membraneK pumpExcretionReabsorptionSecretionPivotal roleVacuolar H-ATPaseH-ATPaseTubulesAcid 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 Research
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 ResearchConceptsNa/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
1992
Long-term activation of protein kinase c causes chronic Na/H antiporter stimulation in cultured proximal tubule cells.
Horie S, Moe O, Miller RT, Alpern RJ. Long-term activation of protein kinase c causes chronic Na/H antiporter stimulation in cultured proximal tubule cells. Journal Of Clinical Investigation 1992, 89: 365-372. PMID: 1310692, PMCID: PMC442861, DOI: 10.1172/jci115594.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityProximal tubule cellsCultured proximal tubule cellsLong-term activationTubule cellsProtein kinase CShort-term activationDose-dependent increaseKinase CActivity 24 hActinomycin DAntiporter activityNa/H antiporterChronic conditionsTwo- to threefold increaseAcute increaseEffect of phorbolProtein kinase C activationChronic effectsTransient increaseMicroM cycloheximidePersistent increaseAlpha-PMAKinase C activationChronic regulator
1991
Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts.
Moe OW, Miller RT, Horie S, Cano A, Preisig PA, Alpern RJ. Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts. Journal Of Clinical Investigation 1991, 88: 1703-1708. PMID: 1658050, PMCID: PMC295708, DOI: 10.1172/jci115487.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityRenal tubule cellsNa/H antiporterMCT cellsRenal epithelial cellsTubule cellsCell linesCultured renal tubule cellsEpithelial cellsMRNA abundanceOpossum kidney cell lineChronic metabolic acidosisAcid preincubationTubule cell lineRat renal cortexH antiporterAntiporter activityUnderlying molecular mechanismsDifferential regulationMetabolic acidosisRenal cortexAcidotic environmentAcid feedingAdaptive increaseKidney cell lineChronic adaptations in proximal tubular H/HCO3 transporters.
Alpern RJ, Horie S, Moe O, Tejedor A, Miller RT, Preisig PA. Chronic adaptations in proximal tubular H/HCO3 transporters. Kidney International Supplement 1991, 33: s29-32. PMID: 1653870.Peer-Reviewed Original ResearchConceptsCultured proximal tubule cellsChronic hyperfiltrationNa/H antiporterProximal tubule cellsChronic acidosisTubule cellsNa/H antiporter activityH antiporterK deficiencyEffect of acidosisExtracellular fluid pHChronic adaptationsAcidosisHyperfiltrationCotransporter activityAbundance of mRNAParallel increaseHCO3- transportersAcid preincubationDeficiencyFluid pHCellsAntiporter activityProtein synthesisExtracellular signalsIncreased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy.
Preisig PA, Alpern RJ. Increased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy. The Journal Of General Physiology 1991, 97: 195-217. PMID: 1849958, PMCID: PMC2216475, DOI: 10.1085/jgp.97.2.195.Peer-Reviewed Original ResearchConceptsHyperfiltration groupChronic hyperfiltrationNa/H antiporterKidney weightCell hypertrophyHigher glomerular filtration rateNa/H antiporter activityH antiporterGlomerular filtration rateVivo microperfused rat proximal tubuleCell pHRat proximal tubuleSymporter activityFiltration rateProximal tubulesUltrafiltrate-like solutionHyperfiltrationSteady-state cell pHProtein feedingPeritubular perfusateDietary proteinParallel increaseUninephrectomyHypertrophyCell acidification
1988
Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule.
Preisig PA, Alpern RJ. Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule. Journal Of Clinical Investigation 1988, 82: 1445-1453. PMID: 2844858, PMCID: PMC442703, DOI: 10.1172/jci113750.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisNa/H antiporterMetabolic acidosisAcidotic animalsH antiporterVivo microperfused rat proximal tubuleDpHi/dtRat proximal tubuleBasolateral membraneTransporter activityDietary acidPeritubular capillariesProximal tubulesNa/HPH-sensitive fluorescent dyeAcidosisTubulesSubsequent studiesAnimalsCarboxy-fluoresceinAbsence of contactCells
1987
Basolateral membrane Na/base cotransport is dependent on CO2/HCO3 in the proximal convoluted tubule.
Krapf R, Alpern RJ, Rector FC, Berry CA. Basolateral membrane Na/base cotransport is dependent on CO2/HCO3 in the proximal convoluted tubule. The Journal Of General Physiology 1987, 90: 833-853. PMID: 2831294, PMCID: PMC2228880, DOI: 10.1085/jgp.90.6.833.Peer-Reviewed Original Research