Alternative channels for urea in the inner medulla of the rat kidney
Published online on September 30, 2015
Abstract
The ascending thin limbs (ATLs) and lower descending thin limbs (DTLs) of Henle's loop in the inner medulla of the rat are highly permeable to urea and yet no urea transporters have been identified in these sections. We hypothesized that novel, yet unidentified transporters in these tubule segments could explain the high urea permeability. cDNAs encoding for SGLT1a, NaGLT1, UT-A2c, and UT-A2d were isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel amino-terminal truncated variant of the Na+-glucose transporter, SGLT1. NaGLT1 is another Na+-glucose transporter primarily located in the proximal tubules and not previously described in the thin limbs. UT-A2c and UT-A2d are novel variants of the urea transporter, UT-A2. UT-A2c is truncated at the carboxyl terminus and UT-A2d has one exon skipped. When rats underwent water restriction for 72 h, mRNA levels of SGLT1a increased in the ATLs, NaGLT1 levels increased in both ATLs and DTLs and UT-A2c increased in the ATLs. [14C]urea uptake assays performed on Xenopus oocytes heterologously expressing these proteins revealed that despite having structural differences from their full-length versions, SGLT1a, UT-A2c and UT-A2d enhanced urea uptake. NaGLT1 also facilitated urea uptake. Uptakes were Na+-independent and inhibitable by phloretin and/or phloridzin. Our data indicate that there are several alternative channels for urea in the rat inner medulla that could potentially contribute to the high urea permeabilities in the thin limb segments.