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Am J Physiol Renal Physiol 278: F52-F62, 2000;
0363-6127/00 $5.00
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Vol. 278, Issue 1, F52-F62, January 2000

UT-A2: a 55-kDa urea transporter in thin descending limb whose abundance is regulated by vasopressin

J. B. Wade1, A. J. Lee1, J. Liu1, C. A. Ecelbarger3, C. Mitchell3, A. D. Bradford3, J. Terris2,3, G.-H. Kim3, and M. A. Knepper3

1 Department of Physiology, Univ. of Maryland School of Medicine, Baltimore 21201; 2 Department of Physiology, Uniformed Services of the Health Sciences, Bethesda 20814; and 3 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892

The renal urea transporter gene (UT-A) produces different transcripts in the inner medullary collecting ducts (UT-A1) and thin descending limbs of Henle's loop (UT-A2), coding for distinct proteins. Peptide-directed rabbit polyclonal antibodies were used to identify the UT-A2 protein in renal medulla of mouse and rat. In the inner stripe of outer medulla, an antibody directed to the COOH terminus of UT-A recognized a membrane protein of 55 kDa. The abundance of this 55-kDa protein was strongly increased in response to chronic infusion of the vasopressin analog 1-deamino-[8-D-arginine]vasopressin (DDAVP) in Brattleboro rats, consistent with previous evidence that UT-A2 mRNA abundance is markedly increased. Immunofluorescence labeling with the COOH-terminal antibody in Brattleboro rats revealed labeling in the lower portion of descending limbs from short-looped nephrons (in the aquaporin-1-negative portion of this segment). This UT-A labeling was increased in response to DDAVP. Increased labeling was also seen in descending limbs of long-looped nephrons in the base of the inner medulla. These results indicate that UT-A2 is expressed as a 55-kDa protein in portions of the thin descending limbs of Henle's loop and that the abundance of this protein is strongly upregulated by vasopressin.

loop of Henle; urinary concentrating mechanism; urea channel; aquaporin-1


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