Alternative Channels for Urea in the Inner Medulla of the Rat Kidney

Am J Physiol Renal Physiol. 2015 Dec 1;309(11):F916-24. doi: 10.1152/ajprenal.00392.2015. Epub 2015 Sep 30.

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 Na(+)-glucose transporter 1a (SGLT1a), Na(+)-glucose transporter 1 (NaGLT1), urea transporter (UT)-A2c, and UT-A2d were isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel NH2-terminal truncated variant of SGLT1. NaGLT1 is a Na(+)-dependent 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 UT-A2. UT-A2c is truncated at the COOH terminus, and UT-A2d has one exon skipped. When rats underwent water restriction for 72 h, mRNA levels of SGLT1a increased in ATLs, NaGLT1 levels increased in both ATLs and DTLs, and UT-A2c increased in ATLs. [(14)C]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 thin limb segments.

Keywords: Xenopus oocytes; gene expression; thin limbs of Henle's loop; urea transport.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Dehydration / genetics
  • Dehydration / metabolism
  • Female
  • Gene Expression Regulation
  • Kidney Medulla / drug effects
  • Kidney Medulla / metabolism*
  • Loop of Henle / drug effects
  • Loop of Henle / metabolism*
  • Male
  • Membrane Transport Modulators / pharmacology
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Osmolar Concentration
  • Permeability
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism*
  • Time Factors
  • Transcription, Genetic
  • Urea / metabolism*
  • Xenopus

Substances

  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • RNA, Messenger
  • Slc5a1 protein, rat
  • Sodium-Glucose Transporter 1
  • urea transporter
  • Urea