Expression of salt and urea transporters in rat kidney during cisplatin-induced polyuria.
BACKGROUND
Cisplatin (CP) induced polyuria in rats is associated with a reduction in medullary hypertonicity, normally generated by the thick ascending 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 CP-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 sacrifice. 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 osmolality. Western analysis of kidney homogenates revealed a marked reduction in band density of the bumetanide-sensitive Na-K-2Cl cotransporter in cortex (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 renal outer medullary potassium channel (ROMK), the type III Na-H exchanger (NHE3), the alpha-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 proteins in the OM of CP-treated rats was different from the control rats, suggesting a qualitative modification of these proteins.


CONCLUSIONS
Changes in the abundance of outer or inner medullary salt or urea transporters are unlikely to play a role in the CP-induced reduction in medullary hypertonicity. However, qualitative changes in UT proteins may affect their functionality and thus may have a role.
Ecelbarger
C A
CA
Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University, Washington D.C., USA.
Sands
J M
JM
Doran
J J
JJ
Cacini
W
W
Kishore
B K
BK
D000818:Animals; D000970:Antineoplastic Agents; D001806:Blood Urea Nitrogen; D015152:Blotting, Northern; D001835:Body Weight; D002352:Carrier Proteins / Q000378:metabolism*; D002945:Cisplatin; D015151:Immunoblotting; D007668:Kidney / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D010984:Platinum / Q000493:pharmacokinetics; D011141:Polyuria / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism*; D014556:Urine / Q000737:chemistry; D000096982:Urea Transporters
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D002945:Cisplatin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010984:Platinum; D012965:Sodium Chloride; D000096982:Urea Transporters