Expression of salt and urea transporters in rat kidney during cisplatin-induced polyuria

Background. Cisplatin (CP) induced polyuria in rats is associated with a re duction in medullary hypertonicity, normally generated by the thick ascendi ng limb (TAL) salt transporters, and the collecting duct urea transporters (UT). To investigate the molecular basis of this abnormality, we determined the protein abundance of major salt and UT isoforms in rat kidney during C P-induced polyuria. Methods. Male Sprague-Dawley rats received either a single injection of CP (5 mg/kg, N = 6) or saline (N = 6) intraperitoneally five days before sacri fice. Urine, blood, and kidneys were collected and analyzed. Results. CP-treated rats developed polyuric acute renal failure as assessed by increased blood urea nitrogen (BUN), urine volume and decreased urine o smolality. Western analysis of kidney homogenates revealed a marked reducti on in band density of the bumetanide-sensitive Na-K-2Cl cotransporter in co rtex (60% of control values, P < 0.05), but not in outer medulla (OM) (106% of control values). There were no differences in band densities for the re nal outer medullary potassium channel (ROMK), the type III Na-H exchanger ( NHE3), the a-subunit of Na,K-ATPase in the OM; or for UT-A1, UT-A2 or UT-A4 in outer or inner medulla. However, the band pattern of UT-A2 and UT-A4 pr oteins in the OM of CP-treated rats was different from the control rats, su ggesting a qualitative modification of these proteins. Conclusions. Changes in the abundance of outer or inner medullary salt or u rea transporters are unlikely to play a role in the CP-induced reduction in medullary hypertonicity. However, qualitative changes in UT proteins may a ffect their functionality and thus may have a role.