New concepts on urea transport by facilitated diffusion.

The end item of the metabolism of proteins generates several wastes. Considering the proportion of proteins that contains a diet balanced in relation to the other nutrients and minerals, the urea represents the 40-50% of all the urinary solutes. The urea is fundamental for the conservation of the corporal water due to its important contribution in the internal renal medulla in the production of urine concentrated. Nevertheless, the time of transit of the tubular fluid thought collector tubule or by the erythrocytes through visa recta is not sufficient so that the urea one reaches a balance by simple diffusion or paracelular transport. Then, both, the internal medullar collecting tubule and the erythrocytes need a facilitated transport for urea that makes a fast movement sufficient to produce urine concentrated. In the last 12 years, at least 7 transporters of urea (UT) have been cloned, 5 of which they are expressed in the kidney. 2 different subfamilies from transporting proteins for urea exist: UT-A and UT-B. Until the present they are 6 isoforms decrypted from UT-A. UT-A I is expressed in the apical membrane of the IMCT. UT-A2 however, is expressed in descendent thin loop of Henle and is involved in the recycled of urea. UT-A3 is expressed in the basal membrane of the IMCT and along with UT-A1 reabsorbs urea from the tubular lumen. UT-A4 is expressed in external renal medulla, although the exact tubular location is not even known UT-A5 has been cloned only of mouse and this expressed in testis. UT-A6 has been identified in colonic mucosa. All isoforms are similar due to the UT-A gene is larger and gives rise to at least these isoforms (splice variants) due to two promoter sites (alternative transcriptional start sites). In rats two sequences of UT-B have been identified: UT-B I and UT-B2 Until the present are not clear if they correspond to two different isoforms, nevertheless, the mRNA of both is present in kidney in endothelial cells not fenestrated of descending vasa recta and in a great variety of organs. UT-B it transports urea and also it works like a water channel. UT-A presents fast mechanisms of regulation like the vasopressin, the hiperosmolarity and the angiotensine. The regulation mechanisms in the long term also involve the vasopressin, in addition to lithium, glucocorticoids and certain pathologies like the s diabetes mellitus, the expansion of volume and the renal insufficiency. Also it has been described an active transport of urea: a secretory antiport sodium-urea in the apical membrane of the IMCT. This active secretion completely is abolished with hypoprotein diets, hypercalcemia or treatments with furosemide. A reabsortive uniport sodium-urea located in the apical membrane of IMCT and also a reabsortive antiport sodium-urea in the basolateral membrane of IMCT has been in cases of hypoprotein diet. These mechanisms have not been cloned yet. In the last years has occurred a great impulse to the knowledge of UT and its possible mechanisms of regulation. An important number of works talks about to the importance of the expression of UT in renal medulla in physiological and physiopathological conditions. It is possible that with the passage of time aberrant mechanisms will be known that modulate their expression and may be involved in pathological processes or as resulting from pharmacological treatments.