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Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter.

G Gamba·S N Saltzberg·M Lombardi·A Miyanoshita·J Lytton·M A Hediger·B M Brenner·S C Hebert
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Abstract

Electroneutral Na+:Cl- cotransport systems are involved in a number of important physiological processes including salt absorption and secretion by epithelia and cell volume regulation. One group of Na+:Cl- cotransporters is specifically inhibited by the benzothiadiazine (thiazide) class of diuretic agents and can be distinguished from Na+:K+:2Cl- cotransporters based on a lack of K+ requirement and insensitivity to sulfamoylbenzoic acid diruetics like bumetanide. We report here the isolation of a cDNA encoding a thiazide-sensitive, electroneutral sodium-chloride cotransporter from the winter flounder urinary bladder using an expression cloning strategy. The pharmacological and kinetic characteristics of the cloned cotransporter are consistent with the properties of native thiazide-sensitive sodium-chloride cotransporters in teleost urinary bladder and mammalian renal distal tubule epithelia. The nucleotide sequence predicts a protein of 1023 amino acids (112 kDa) with 12 putative membrane-spanning regions, which is not related to other previously cloned sodium or chloride transporters. Northern hybridization shows two different gene products: a 3.7-kb mRNA localized only to the urinary bladder and a 3.0-kb mRNA present in several non-bladder/kidney tissues.

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Amino Acid SequenceAnimalsBase SequenceBenzothiadiazinesCarrier ProteinsDNAFlounderIntestinesKineticsModels, StructuralMolecular Sequence DataOocytesOpen Reading FramesOrgan SpecificityProtein Structure, SecondaryRecombinant ProteinsSodiumSodium Chloride SymportersSymportersUrinary BladderXenopus laevisJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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G Gamba, S N Saltzberg, M Lombardi, A Miyanoshita, J Lytton, M A Hediger, B M Brenner, S C Hebert. 1993-04-01. Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter.. https://doi.org/10.1073/pnas.90.7.2749

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