EVIDENCE FOR DISTINCT VASCULAR AND TUBULAR UREA TRANSPORTERS IN THE RAT-KIDNEY

Facilitated urea transport has been demonstrated in several mammalian tissues, including those of the collecting ducts and red blood cells. Two urea transporters have been recently cloned: UT2, expressed in rab bit inner medullary collecting ducts, and HUT11, expressed in human er ythrocytes. Because of significant identity (63%) between these two tr ansporters, and because HUT11 is also expressed in the human kidney, t hey could represent the same transporter with species-related differen ces in their sequences. In the study presented here, two different cDN A fragments, corresponding to the rat equivalents (rUT2 and rUT11) of the two previously cloned urea transporters, were isolated by reverse transcription-polymerase chain reaction. These rat probes were used fo r Northern analysis of RNA extracted from rat tissues. From the follow ing findings, the results show that rUT2 and rUT11 are two distinct ur ea transporters: (1) The two cDNA fragments isolated in the rat exhibi t different sequences; (2) The mRNA for rUT2 is found exclusively in t he kidney, with two transcripts (3.2- and 4.4-kilobase (kb)), whereas rUT11 (only one transcript, 4.2 kb) is present in the brain, spleen, k idney, and testis; (3) In the kidney, the inner stripe of the outer me dulla expresses rUT11 mRNA and the short transcript of rUT2, whereas t he inner medulla expresses rUT11 and the two rUT2 transcripts; (4) In hydronephrotic kidneys that have completely lost their tubular epithel ium but have intact vasculature, rUT2 transcripts are no longer expres sed, whereas expression of rUT11 is intensified; (5) Experimental chro nic alterations in urine concentrating activity induced different chan ges in the expression of rUT2 and rUT11.