Early selective effects of gentamicin on renal brush-border membrane Na-Pi cotransport and Na-H exchange.
Gentamicin nephrotoxicity is associated with impairments in proximal tubular function. This study determined whether gentamicin administration to the rat, before a reduction in glomerular filtration rate (GFR), causes early and selective alterations in renal cortical brush-border membrane (BBM) enzyme and transport activity, lipid composition, and fluidity. Three days of gentamicin administration caused significant decreases in the Vmax of alkaline phosphatase, the Vmax of sodium gradient-dependent phosphate transport (Na-Pi cotransport), and the Vmax of pH gradient-dependent sodium transport (Na-H exchange). Gentamicin did not affect BBM-bound maltase or leucine aminopeptidase activities and sodium gradient-dependent glucose or proline transport activities. Gentamicin also caused a significant decrease in BBM sphingomyelin, significant increases in BBM phosphatidylcholine and phosphatidylinositol, a significant decrease in the phospholipid fatty acid saturation index, and a significant increase in BBM fluidity, i.e., decrease in the fluorescence anisotropy of diphenylhexatriene. These BBM functional and compositional effects of gentamicin were independent of endogenous parathyroid hormone activity. We conclude that gentamicin causes early and specific alterations in BBM enzyme and transport activity and also lipid composition, which may play an important role in the progression of renal cell injury.
Levi
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Cronin
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D017245:Foscarnet; D005839:Gentamicins / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D008871:Microvilli / Q000201:enzymology / Q000378:metabolism; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D005839:Gentamicins; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D017245:Foscarnet; D010746:Phosphonoacetic Acid