2008
Na-K-Cl Cotransporter-1 in the Mechanism of Ammonia-induced Astrocyte Swelling*
Jayakumar A, Liu M, Moriyama M, Ramakrishnan R, Forbush B, Reddy P, Norenberg M. Na-K-Cl Cotransporter-1 in the Mechanism of Ammonia-induced Astrocyte Swelling*. Journal Of Biological Chemistry 2008, 283: 33874-33882. PMID: 18849345, PMCID: PMC2590687, DOI: 10.1074/jbc.m804016200.Peer-Reviewed Original ResearchConceptsNKCC activityNa-K-ClAstrocyte swellingCell swellingNa-K-Cl cotransporter-1Na-K-Cl cotransporterComplication of acute liver failureN-nitro-L-arginine methyl esterNitric oxide synthase inhibitionActivation of NKCC1NKCC1 protein expressionCultured astrocytesInduce oxidative/nitrosative stressAcute liver failureLoss of ion homeostasisSwelling of astrocytesPhosphorylated NKCC1NKCC1 expressionLiver failureNKCC1Synthase inhibitionBrain herniationBrain edemaIntracranial pressureProtein expression
2000
The Na-K-Cl Cotransporter of Secretory Epithelia
Haas M, Forbush B. The Na-K-Cl Cotransporter of Secretory Epithelia. Annual Review Of Physiology 2000, 62: 515-534. PMID: 10845101, DOI: 10.1146/annurev.physiol.62.1.515.Peer-Reviewed Original ResearchConceptsNa-K-ClNa-K-Cl cotransporterRegulation of NKCC1Secretory epitheliaNa-K-Cl cotransporter isoformsK-Cl cotransporter isoformsApical Cl- channelsNa-Cl cotransporterNon-epithelial cellsNKCC1 regulationCl- channelsBasolateral membraneCotransporter proteinFluid secretionNKCC isoformsNKCC1Ascending limbHenle's loopEpithelial cellsMacula densaIon transport proteinsTransport NaEpitheliaCotransporterCell volume
1999
Functional interaction of the K-Cl cotransporter (KCC1) with the Na-K-Cl cotransporter in HEK-293 cells
Gillen C, Forbush B. Functional interaction of the K-Cl cotransporter (KCC1) with the Na-K-Cl cotransporter in HEK-293 cells. American Journal Of Physiology 1999, 276: c328-c336. PMID: 9950760, DOI: 10.1152/ajpcell.1999.276.2.c328.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-Cl cotransport activityNa-K-ClK-Cl cotransportHEK-293 cellsCotransport activityK-ClHEK-293Activation of Na-K-Cl cotransportCell swellingK-Cl cotransport activityHypotonic cell swellingIntracellular Cl- concentrationFunctional interactionsKCC1External KCotransporterIon-transporting epitheliaCell linesN-ethylmaleimidePhysiological rangeCellsInvestigate functional interactionsCross-talkPretreatment
1998
Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding
Isenring P, Jacoby S, Chang J, Forbush B. Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding. The Journal Of General Physiology 1998, 112: 549-558. PMID: 9806964, PMCID: PMC2229443, DOI: 10.1085/jgp.112.5.549.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBumetanideCarrier ProteinsCells, CulturedChloridesDiureticsHumansKidneyKineticsMutagenesis, Site-DirectedOligonucleotide ProbesPotassiumProtein Structure, TertiaryRecombinant Fusion ProteinsRubidium RadioisotopesSharksSodiumSodium-Potassium-Chloride SymportersSpecies SpecificityThe role of transmembrane domain 2 in cation transport by the Na–K–Cl cotransporter
Isenring P, Jacoby S, Forbush B. The role of transmembrane domain 2 in cation transport by the Na–K–Cl cotransporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 7179-7184. PMID: 9618559, PMCID: PMC22778, DOI: 10.1073/pnas.95.12.7179.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterBumetanide-sensitive 86Rb influxTransmembrane domain 2Na-Cl cotransporterBumetanide bindingNa-K-ClHEK-293 cellsHuman cotransportersDomain 2Third transmembrane domainCotransporterNa affinityHEK-293Stable transfectionNKCC2BumetanideCation transportTransmembrane domain 3Transmembrane domainDomain 3Alternative splicingIon transportComparison of Na-K-Cl Cotransporters NKCC1, NKCC2, AND THE HEK CELL Na-K-Cl COTRANSPORTER*
Isenring P, Jacoby S, Payne J, Forbush B. Comparison of Na-K-Cl Cotransporters NKCC1, NKCC2, AND THE HEK CELL Na-K-Cl COTRANSPORTER*. Journal Of Biological Chemistry 1998, 273: 11295-11301. PMID: 9556622, DOI: 10.1074/jbc.273.18.11295.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterHEK-293 cellsNa-K-Cl cotransporter NKCC1Epithelial cellsBasolateral Cl- exitHEK-293Reverse transcriptase-polymerase chain reactionNa-K-ClRenal epithelial cellsEpithelial Cl- transportResting level of activityMaintenance of cell volumeSecretory epithelial cellsInhibitor bumetanideCotransporter NKCC1NKCC2 activityCl- exitNKCC1Cl- transportNKCC2CotransporterVolume responseNa affinityResting levelBumetanideThe Na-K-Cl Cotransporters
Haas M, Forbush B. The Na-K-Cl Cotransporters. Journal Of Bioenergetics And Biomembranes 1998, 30: 161-172. PMID: 9672238, DOI: 10.1023/a:1020521308985.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClNa-K-Cl cotransport activityNa-K-Cl cotransporter isoformsCotransport activitySecretory epitheliaApical Cl- channelsHypokalemic metabolic alkalosisCation-chloride cotransportersNKCC2 geneCl- channelsBartter's syndromeVolume depletionBasolateral membraneCotransporter proteinApical membraneSalt wastingMetabolic alkalosisSecreting epitheliaNonepithelial cellsAscending limbHenle's loopK-ClCotransporterEpithelial cells
1997
Ion and Bumetanide Binding by the Na-K-Cl Cotransporter
Isenring P, Forbush B. Ion and Bumetanide Binding by the Na-K-Cl Cotransporter. Journal Of Biological Chemistry 1997, 272: 24556-24562. PMID: 9305921, DOI: 10.1074/jbc.272.39.24556.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClBumetanide-sensitive 86Rb influxCation-chloride cotransporter familyApparent affinityHEK-293 cellsInhibitor bumetanideCell surface deliveryElectrolyte secretionTime course of activationBumetanidePolarized epitheliaBumetanide bindingCotransporterCl- mediumCotransported ionsHEK-293SNKCC1Hydrophobic central domainSurface deliveryCourse of activationCentral domainTime courseCytoplasmic N-Chimera approach
1996
Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human A NEW MEMBER OF THE CATION-CHLORIDE COTRANSPORTER FAMILY*
Gillen C, Brill S, Payne J, Forbush B. Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human A NEW MEMBER OF THE CATION-CHLORIDE COTRANSPORTER FAMILY*. Journal Of Biological Chemistry 1996, 271: 16237-16244. PMID: 8663127, DOI: 10.1074/jbc.271.27.16237.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCarrier ProteinsCell LineChloridesCloning, MolecularDatabases, FactualDNA PrimersDNA, ComplementaryHumansKidneyKineticsModels, StructuralMolecular Sequence DataMultigene FamilyOpen Reading FramesPhylogenyPolymerase Chain ReactionPotassiumProtein Structure, SecondaryRabbitsRatsRecombinant ProteinsRubidiumSequence Homology, Amino AcidSequence Tagged SitesSymportersTransfectionConceptsNa-K-Cl cotransporterK-Cl cotransportK-ClRat brain cDNA libraryThiazide-sensitive Na-Cl cotransporterRate of 86Rb effluxBrain cDNA libraryBumetanide-sensitive Na-K-Cl cotransporterN-linked glycosylation sitesC-terminal regionSubstantial sequence homologyNa-Cl cotransporterNa-K-ClHEK 293) cellsUptake of 86RbNorthern blot analysisGenome sequenceCDNA libraryHydropathy analysisFunctional expressionSequence homologyReverse transcription-polymerase chain reactionHuman embryonic kidneySequence analysisHomologous cDNA probesImmunocytochemical studies of the Na-K-Cl cotransporter of shark kidney
Biemesderfer D, Payne J, Lytle C, Forbush B. Immunocytochemical studies of the Na-K-Cl cotransporter of shark kidney. American Journal Of Physiology 1996, 270: f927-f936. PMID: 8764311, DOI: 10.1152/ajprenal.1996.270.6.f927.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClBasolateral membraneCotransporter proteinBasolateral membranes of proximal tubulesNa-K-Cl cotransport proteinShark kidneyBasolateral plasma membraneDistal tubule segmentsApical plasma membraneShark rectal glandDistal nephronReabsorptive epitheliaNaCl reabsorptionPlasma membraneWestern blot analysisTubule segmentsProximal tubulesDiluting segmentWeak stainingShark Squalus acanthiasPresence of multiple isoformsDogfish shark Squalus acanthiasCotransporterMonoclonal antibodiesRegulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl
Lytle C, Forbush B. Regulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl. American Journal Of Physiology 1996, 270: c437-c448. PMID: 8779905, DOI: 10.1152/ajpcell.1996.270.2.c437.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClCotransport activityNa-K-Cl cotransport proteinResponse to cell shrinkageIncreased cotransport activityExtracellular K concentrationBlocking activityRefractory to forskolinPhosphatase inhibitor calyculin AInhibitor calyculin AShark rectal glandCotransporter proteinCytoplasmic Cl-CotransporterCell ClSecretory stimuliCell shrinkageCalyculin APhosphorylationRate of entryRegulatory phosphorylationPhosphorylation stateSecretory tubulesRectal gland
1995
Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies
Lytle C, Xu J, Biemesderfer D, Forbush B. Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies. American Journal Of Physiology 1995, 269: c1496-c1505. PMID: 8572179, DOI: 10.1152/ajpcell.1995.269.6.c1496.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-Cl cotransport proteinNa-K-ClMonoclonal antibodiesEpithelial salt transportCell volume homeostasisT antibodyAscending limb cellsImmunoreactive proteinBinding site densityChloride reabsorptionChloride secretionBasolateral marginsParotid glandCotransporter proteinApical membraneWestern blot analysisVolume homeostasisAcinar cellsWestern blot analysis of membranesCotransporterImmunocytochemical studiesRabbit kidneyAmount of immunoreactive proteinRabbit parotid glandPrimary Structure, Functional Expression, and Chromosomal Localization of the Bumetanide-sensitive Na-K-Cl Cotransporter in Human Colon *
Payne J, Xu J, Haas M, Lytle C, Ward D, Forbush B. Primary Structure, Functional Expression, and Chromosomal Localization of the Bumetanide-sensitive Na-K-Cl Cotransporter in Human Colon *. Journal Of Biological Chemistry 1995, 270: 17977-17985. PMID: 7629105, DOI: 10.1074/jbc.270.30.17977.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlotting, NorthernBumetanideCarrier ProteinsCell LineChloridesChromosome MappingChromosomes, Human, Pair 5Cloning, MolecularColonDNA, ComplementaryHumansMolecular Sequence DataPotassiumProtein ConformationSodiumSodium-Potassium-Chloride SymportersTumor Cells, CulturedConceptsNa-K-Cl cotransporterT84 cellsRenal Na-K-Cl cotransporterThiazide-sensitive Na-Cl cotransporterBumetanide-sensitive 86Rb influxBumetanide-sensitive Na-K-Cl cotransporterNa-Cl cotransporterHuman colon carcinoma lineNa-K-ClColon carcinoma linePrimary structureHuman embryonic kidney cellsChloride-free mediumShark rectal glandProtein kinase AStably transfected cellsG + C contentEmbryonic kidney cellsElectroneutral cotransporterUrinary bladderCarcinoma linesAbsorptive epitheliaSNKCC1Screening cDNA librariesBiotin-labeled cDNAMolecular characterization of the epithelial NaKCl cotransporter isoforms
Payne J, Forbush B. Molecular characterization of the epithelial NaKCl cotransporter isoforms. Current Opinion In Cell Biology 1995, 7: 493-503. PMID: 7495568, DOI: 10.1016/0955-0674(95)80005-0.Peer-Reviewed Original Research
1994
Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter.
Xu J, Lytle C, Zhu T, Payne J, Benz E, Forbush B. Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 2201-2205. PMID: 8134373, PMCID: PMC43338, DOI: 10.1073/pnas.91.6.2201.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterBumetanide-sensitive Na-K-Cl cotransporterNa-K-ClNa-K-Cl cotransport activityNa-K-Cl cotransport proteinThiazide-sensitive Na-Cl cotransporterCoupled movement of NaUncharacterized genesShort stretches of homologyRegulation of ionic balanceStretches of homologyC. elegans cDNAHEK-293 cellsHuman HEK-293 cellsPutative transmembrane domainsBumetanide sensitivityCotransport activityCotransporter proteinMovement of NaUrinary bladderAbsorptive epitheliaNorthern blot analysisPhosphoacceptor residuesCDNA sequenceCoding region
1992
The Na-K-Cl cotransporter of avian salt gland. Phosphorylation in response to cAMP-dependent and calcium-dependent secretogogues.
Torchia J, Lytle C, Pon D, Forbush B, Sen A. The Na-K-Cl cotransporter of avian salt gland. Phosphorylation in response to cAMP-dependent and calcium-dependent secretogogues. Journal Of Biological Chemistry 1992, 267: 25444-25450. PMID: 1281159, DOI: 10.1016/s0021-9258(19)74061-7.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-3-isobutylxanthine8-Bromo Cyclic Adenosine MonophosphateAnimalsBlotting, WesternCalciumCarbacholCarrier ProteinsCell MembraneColforsinCyclic AMPDucksKineticsMembrane ProteinsPhosphatesPhosphorylationSalt GlandSodium-Potassium-Chloride SymportersTime FactorsVasoactive Intestinal PeptideConceptsNa-K-Cl cotransporterPhosphorylation of pp170Avian salt glandMonoclonal antibodiesResponse to carbacholEffect of forskolinNa-K-ClIntact cell preparationsConcentration-dependent increaseStimulation of secretionIncreased approximately 5-foldCAMP accumulationExposure of cellsCAMP-dependent protein kinasePp170Approximately 5-foldCell preparationsCAMP-dependentSalt gland cellsGland membranesWestern blottingForskolinSecretogoguesVIPAntibodiesThe Na-K-Cl cotransport protein of shark rectal gland. I. Development of monoclonal antibodies, immunoaffinity purification, and partial biochemical characterization.
Lytle C, Xu J, Biemesderfer D, Haas M, Forbush B. The Na-K-Cl cotransport protein of shark rectal gland. I. Development of monoclonal antibodies, immunoaffinity purification, and partial biochemical characterization. Journal Of Biological Chemistry 1992, 267: 25428-25437. PMID: 1460038, DOI: 10.1016/s0021-9258(19)74059-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, MonoclonalBenzophenonesBlotting, WesternCarrier ProteinsCell MembraneChloridesCholic AcidsChromatography, AffinityChromatography, High Pressure LiquidChromatography, Ion ExchangeDogfishElectrophoresis, Polyacrylamide GelFluorescent Antibody TechniqueMembrane ProteinsMiceMice, Inbred BALB CMolecular Sequence DataMolecular WeightPeptide FragmentsPotassiumRectumSebaceous GlandsSodiumSodium-Potassium-Chloride SymportersSulfanilamidesConceptsNa-K-Cl cotransport proteinNa-K-ClCotransporter proteinNa-K-Cl cotransporterMonoclonal antibodiesShark rectal glandLoop diureticsBasolateral membraneApical membraneTransport of NaRepresentative antibodiesCotransporterCoupled transport of NaAntibodiesPattern of recognitionTreated with N-glycanaseGland secretory cellsImmunoelectron microscopyCell membranePlasma membraneEpitopesPhysiological evidenceSecretory cellsProteolytic fragmentsThe Na-K-Cl cotransport protein of shark rectal gland. II. Regulation by direct phosphorylation.
Lytle C, Forbush B. The Na-K-Cl cotransport protein of shark rectal gland. II. Regulation by direct phosphorylation. Journal Of Biological Chemistry 1992, 267: 25438-25443. PMID: 1334094, DOI: 10.1016/s0021-9258(19)74060-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCarrier ProteinsChromatography, High Pressure LiquidCyclic AMPDogfishHypertonic SolutionsIsoquinolinesKineticsMembrane ProteinsMolecular Sequence DataPeptide FragmentsPhosphorylationProtein Kinase InhibitorsRectumSebaceous GlandsSodium-Potassium-Chloride SymportersSulfanilamidesThionucleotidesConceptsNa-K-Cl cotransport proteinNa-K-ClCotransporter proteinShark rectal glandCell shrinkageCAMP-dependent secretagoguesRectal gland tubulesOsmotically induced changesCotransporter phosphorylationCotransport activityKinase inhibitorsProtein kinase inhibitorsCotransporterPhosphorylation stateRectal glandActive stateH-8K-252aTubulesGlandPhosphorylationCDNA analysisCellsIncreased 5Protein phosphorylationNa-K-Cl cotransport in the shark rectal gland. II. Regulation in isolated tubules
Lytle C, Forbush B. Na-K-Cl cotransport in the shark rectal gland. II. Regulation in isolated tubules. American Journal Of Physiology 1992, 262: c1009-c1017. PMID: 1314482, DOI: 10.1152/ajpcell.1992.262.4.c1009.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClShark rectal glandInhibitor of Na-K-Cl cotransportApical Cl- channelsCell shrinkageEffects of secretagoguesOsmotically induced changesSensitivity to cAMPCl- channelsExtracellular sodiumIsolated tubulesCotransporterHormonal modulationSecretory stimuliSignal transduction pathwaysSecretagoguesRectal glandTubulesRectal gland secretionHypertonicityCell volumeTransduction pathwaysGlandCellsNa-K-Cl cotransport in the shark rectal gland. I. Regulation in the intact perfused gland
Forbush B, Haas M, Lytle C. Na-K-Cl cotransport in the shark rectal gland. I. Regulation in the intact perfused gland. American Journal Of Physiology 1992, 262: c1000-c1008. PMID: 1566806, DOI: 10.1152/ajpcell.1992.262.4.c1000.Peer-Reviewed Original ResearchConceptsNa-K-ClNa-K-Cl cotransport systemNa-K-Cl cotransporterVasoactive intestinal peptideCotransport systemVIP-stimulated increasesStimulation of secretionShark rectal glandK exitBasolateral membranePerfused glandShark Squalus acanthiasIntestinal peptideArterial-venous differencesDogfish shark Squalus acanthiasIntact glandsPerfusion solutionPerfusion periodBasal statePerfusionGlandInvestigate regulationRectal glandRinger's solutionTime course