Cloning and characterization of two new isoforms of the rat kidney urea transporter: UT-A3 and UT-A4

Alexander Karakashian, Richard T. Timmer, Janet D. Klein, Robert B. Gunn, Jeff M. Sands, Serena M. Bagnasco

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


Urea transport in the kidney is important for the production of concentrated urine and is mediated by a family of transporter proteins, identified from erythropoietic tissue (UT-B) and from kidney (UT-A). Two isoforms of the renal urea transporter (UT-A) have been cloned so far: UT-A1 and UT-A2. We used rapid amplification of cDNA ends to clone two new isoforms of the rat UT-A transporter: UT-A3 and UT-A4. UT-A3 and UT-A4 are 87% homologous. The UT-A3 cDNA encodes a peptide of 460 amino acids, which corresponds to the amino-terminal half of the UT-A1 peptide and is 62% identical to UT-A2. The UT-A4 cDNA encodes a peptide of 466 amino acids, which is 84% identical to UT-A2. Transient transfection of HEK-293 cells with the UT-A3 or UT-A4 cDNA results in phloretin-inhibitable urea uptake, which is increased by forskolin. Thus, both new isoforms encode functional urea transporters that may be vasopressin-regulated. UT-A3 and UT-A4 mRNA are expressed in the renal outer and inner medulla but not in the cortex; unidentified UT-A isoforms similar to UT-A3 may also be expressed in the testis. It is concluded that there are at least four different rat UT-A urea transporters.

Original languageEnglish (US)
Pages (from-to)230-237
Number of pages8
JournalJournal of the American Society of Nephrology
Issue number2
StatePublished - Feb 1999
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


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