FUNCTIONAL-DIFFERENTIATION OF THE HUMAN RED-BLOOD-CELL AND KIDNEY UREA TRANSPORTERS

The recent cloning of two urea transporters will allow to better under stand their role in the urinary concentrating mechanism. This physiolo gical approach needs to be sustained by a knowledge of their functiona l characteristics. We compared the pharmacological properties of the h uman red blood cell and kidney urea transporters (HUT11 and HUT2) in t he Xenopus oocyte expression system. Both proteins allow the rapid tra nsfer of urea but not of water Both are inhibited by phloretin, althou gh with different half-maximal inhibitory concentrations (IC50; 75 mu M for HUT11 and 230 mu M for HUT2). Whereas para-chloromercuribenzene sulfonate inhibits HUT11 with an IC50 of 150 mu M, it does not inhibit HUT2, whatever the concentration used. We demonstrate that thiourea d iffuses through HUT11 with a Michaelis constant (K-m) of 40 mM, but no t through HUT2. In contrast, it inhibits urea transport through both p roteins. This identification of a substrate binding site independent f rom the transport activity is the first step in the understanding of t he molecular events underlying urea transport.