Abstract
We studied the effect of gentamicin on Na +-dependent d-glucose transport into brush-border membrane vesicles isolated from rabbit kidney outer cortex (early proximal tubule) and outer medulla (late proximal tubule) in vitro. We found the same osmotically active space and nonspecific binding between control and gentamicin-treated brush-border membrane vesicles. There was no difference in the passive permeability properties between control and gentamicin-treated brush-border membrane vesicles. Kinetic analyses of d-glucose transport into 1 mM gentamicin-treated brush-border membrane vesicles demonstrated that gentamicin decreased V max in the outer cortical preparation, while it did not affect V max in the outer medullary preparation. With regard to K m, there was no effect of gentamicin in any vesicle preparation. When brush-border membrane vesicles were incubated with higher concentrations of gentamicin, Na +-dependent d-glucose transport was inhibited dose-dependently in both outer cortical and outer medullary preparations. Dixon plots yield inhibition constant K i = 4 mM in the outer cortical preparation and K i = 7 mM in the outer medullary preparation. These results indicate that the Na +-dependent d-glucose transport system in early proximal tubule is more vulnerable to gentamicin toxicity than that in late proximal tubule.
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