Background: The renal reabsorption of natural nucleosides and a variety of nucleoside-derived drugs relies on the function of the apically located, Na(+)-dependent, concentrative nucleoside transporters CNT1, CNT2, and CNT3 (SLC28A1, SLC28A2, and SLC28A3). The aims of this study were to determine the segmental localization of the three SLC28 family members and to establish whether streptozotocin-induced diabetes alters their expression.
Methods: SLC28 expression was measured by real-time polymerase chain reaction (PCR) on microdissected sections of rat nephrons. Diabetes was induced by streptozotocin treatment and the biochemical profiles of control, diabetic, and insulin-treated rats were established. The effect of diabetes on SLC28 expression was assessed in those segments that significantly express SLC28 genes.
Results: CNT1-3 mRNAs were expressed in the proximal tubule and glomerulus. In addition, CNT2 and CNT3 mRNAs were expressed in the outer medullary and cortical collecting duct, respectively. Diabetes reduced expression of the three CNTs in almost all nephron segments, and this effect was not prevented by an insulin treatment that normalized all blood and urine parameters. Diabetes increased CNT1 and CNT3 expression in the glomerulus and insulin treatment decreased it.
Conclusion: The relative distribution of SLC28 gene expression suggests a role for the proximal tubule in renal nucleoside clearance and an accessory role for CNT2 and CNT3, in adenosine-mediated regulation of collecting duct functions. Diabetes probably may impair nucleoside clearance independently of insulin.