Urea transporters are distributed in endothelial cells and mediate inhibition of L-arginine transport.
Our laboratory previously reported that uremic levels of urea inhibit L-arginine (L-Arg) transport into endothelial cells. The present study further investigated this effect. We measured L-Arg transport in cultured bovine aortic endothelial cells with normal or high urea (25 mM). The urea transport inhibitor phloretin abolished the inhibitory effect of urea on L-Arg transport, suggesting a role for urea transporters (UTs). We screened bovine aortic endothelial cells and several other endothelial cell types for the presence of UTs by using Western blot analysis. UT-B was present in all endothelial cells, irrespective of species or location of derivation, whereas UT-A distribution was variable and sparse. UT-B was also abundant in rat aorta, mesenteric blood vessels, and spinotrapezius muscle, whereas UT-A distribution was, again, variable and sparse. Chronic elevation of urea had variable, inconsistent effects on UT abundance. This study showed that urea must enter endothelial cells, probably by UT-B, to inhibit L-Arg transport. In view of the wide distribution of UT-B in rat vasculature, elevated blood urea nitrogen may lead to endothelial L-Arg deficiency in vivo.
Wagner
Laszlo
L
Department of Physiology, West Virginia University, Morgantown, West Virginia 26506-9229, USA.
Klein
Janet D
JD
Sands
Jeff M
JM
Baylis
Chris
C
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis* / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology*; D026901:Membrane Transport Proteins; D018482:Muscle, Skeletal / Q000098:blood supply / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D014508:Urea / Q000494:pharmacology; D014511:Uremia / Q000378:metabolism; D000096982:Urea Transporters
D001120:Arginine; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D014508:Urea; D000096982:Urea Transporters