Molecular cloning and characterization of the renal diuretic-sensitive electroneutral sodium-(potassium)-chloride cotransporters.
cDNAs encoding the two major electroneutral sodium-chloride transporters present in the mammalian kidney, the bumetanide-sensitive Na(+)-K(+)-Cl- symporter and thiazide-sensitive Na(+)-Cl- cotransporter, were isolated and their functional activity characterized in Xenopus laevis oocytes [2]. Although they differ in sensitivities to bumetanide and thiazides and have different requirements for potassium, these approximately 115-kDa proteins share about 60% sequence similarity and exhibit a topology featuring 12 potential membrane-spanning helices flanked by large hydrophilic domains at the NH2- and COOH-termini. These molecules, together with the Na-Cl cotransporter from the flounder urinary bladder, which exhibits a significant homology suggestive of common ancestry, define a new family of electroneutral Na(+)-(K+)-Cl- cotransporters. Northern blot analysis and in situ hybridization indicate that these transporters are expressed predominantly in kidney with an intrarenal distribution consistent with their recognized functional localization. The kidney-specific distribution of transcripts encoding these cotransporters suggest that other, probably related, genes encode non-renal Na(+)-(K+)-Cl- cotransporters.
Harvard Center for Study of Kidney Disease, Harvard Medical School, Boston, MA.
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D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000302:isolation & purification; D002712:Chlorides / Q000378:metabolism; D003001:Cloning, Molecular; D005432:Flounder; D015870:Gene Expression; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D014982:Xenopus laevis
D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D012964:Sodium; D011188:Potassium