Functional differentiation of the human red blood cell and kidney
urea transporters.
Martial, Sonia, Bernadette Oliv[grave]es, Laurence Abrami,
C[acute]ecile Couriaud, Pascal Bailly, Guofeng You, Matthias A.
Hediger, Jean-Pierre Cartron, Pierre Ripoche, and Germain Rousselet.
Service de Biologie Cellulaire, CEA/Saclay, 91191 Gif-sur-Yvette
Cedex, France, INSERM U76, GIP-Institut National de la Transfusion
sanguine, 75015 Paris, France, Harvard Medical School, Brigham and
women's Hospital, Boston, MA 02115, USA
APStracts 3:0169F, 1996.
The recent cloning of two urea transporters will allow to better
understand their role in the urinary concentrating mechanism. This
physiological approach needs to be sustained by a knowledge of their
functional characteristics. We compared the pharmacological
properties of the human red cell and kidney urea transporters (HUT11
and HUT2) in the Xenopus oocyte expression system. Both proteins
allow the rapid transfer of urea, but not of water. Both are
inhibited by phloretin, although with different 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 diffuses through HUT11 with a Km of 40 mM, but not through
HUT2. In contrast, it inhibits urea transport through both proteins.
This identification of a substrate binding site independent from the
transport activity is the first step in the understanding of the
molecular events underlying urea transport.
Received 26 December 1995; accepted in final form 19 September
1996.
APS Manuscript Number F429-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996