THE UREA TRANSPORTERS

Water and urea use different pathways to cross biological membranes. c hannels and carriers. Numerous water channels were cloned (aquaporins) ; only two urea transporters are caracterized in mammalians (UT2 and U T11) with sequence homologies suggesting two different carriers. This was confirmed by different localizations: UT2 was only found in renal medulla and probably was the AVP-sensitive urea carrier while UT11 was found in testis, spleen, brain and kidney and represents the constitu tive urea carrier described in red blood cell. UT2 hybridized two tran scripts, 4.1 kb and 2.9 kb. The large transcript expression was regula ted by low protein diet whereas the short transcript was regulated by hydratation conditions. The heterologous expression into Xenopus oocyt es showed a large increase of the urea uptake (UT2>UT11), inhibitable by phloretin for UT11 and UT2 and by pCMBS only for UT11. A saturable transport of thiourea was only observed into oocytes expressing UT11. Moreover, hUT11 is encoded by the kidd locus, bur, Jk (a-b-) individua ls, in the absence of this urea transporter did not present related pa thology. Other carriers still have to be identified and characterized in different renal segments and other tissues.