Decreased sodium dependent D-glucose transport across renal brush-border membranes in cis-diamminedichloride platinum induced acute renal failure.
Na-coupled D-glucose transport in rabbits with cis-diamminedichloride platinum (CDDP; cisplatin) induced acute renal failure (ARF) has been studied. ARF occurred at 3 days after injection of CDDP (3 mg/kg i.v.). Na-coupled D-glucose transport into brush-border membrane vesicles (BBMV) from both outer cortex (OC) and outer medulla (OM) of ARF rabbits under zero-trans condition was decreased. Increased Km (i.e., decreased affinity of transport carrier for D-glucose) in OC and decreased Vmax (i.e., decreased number of glucose carrier) in OM were observed in CDDP-induced ARF rabbits. Decrease glucose transport was also observed under equilibrium exchange condition. Intravesicular volume of BBMV from OC and OM of ARF rabbits was decreased. In homogenate and BBMV from OC and OM of ARF rabbits, activities of gamma-glutamyl transpeptidase and alkaline phosphatase (marker enzymes of brush-border membrane) were decreased. Activities of succinate dehydrogenase, glucose-6-phosphatase, and Na-K ATPase (marker enzymes of mitochondria, endoplasmic reticulum, and basal lateral membrane, respectively) were not affected by CDDP administration. These results suggested that one of the main target sites of CDDP in kidney is brush-border membrane (BBM) along the proximal tubule, that is, not only Na-coupled D-glucose transport carrier protein but also other proteins in BBM.
Yanase
M
M
Fifth Department of Internal Medicine, Hyogo College of Medicine, Japan.
Uyama
O
O
Nakanishi
T
T
Shiratsuki
N
N
Sugita
M
M
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits
D009004:Monosaccharide Transport Proteins; D005947:Glucose; D002945:Cisplatin