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 compositiion, and fluidity. Three days of gentamicin administration caused significant decreases in the V(max) of alkaline phosphatase, the V(max) of sodium gradient-dependent phosphate transport (Na-P(i) cotransport), and the V(max) 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.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|Issue number||5 27-5|
|State||Published - 1990|
- alkaline phosphatase
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