Gentamicin inhibits carrier-mediated dipeptide transport in the
kidney.
Skopicki, Hal A., Demetrios Zikos, Ernest J. Sukowski, Kenneth A.
Fisher, and Darryl R. Peterson.
DEPARTMENT OF PHYSIOLOGY AND BIOPHYSICS AND DEPARTMENT OF MEDICINE,
FINCH UNIVERSITY OF HEALTH SCIENCE/THE CHICAGO MEDICAL SCHOOL, NORTH
CHICAGO, IL 60064, AND DEPARTMENT OF MEDICINE, CHRIST HOSPITAL AND
MEDICAL CENTER, OAK LAWN, IL 60453
APStracts 2:0160F, 1995.
The effect of gentamicin on transport of pyroglutamyl-histidine (pGlu
-His) was examined in rabbit renal brush border membrane vesicles.
Gentamicin, an aminoglycoside antibiotic, is limited in its usage
because of nephrotoxicity characterized in part by transport defects
in the proximal tubule. Since there is no information regarding the
effects of gentamicin on renal peptide carriers, uptake of [3H]pGlu
-His was measured in brush border membrane vesicles following either
in vivo or in vitro exposure to the antibiotic. One hour after in
vivo administration, the Vmax for pGlu-His transport was
significantly reduced in isolated membrane vesicles washed free of
the drug, but the apparent Km was unaltered. Co-incubation of
membranes with gentamicin during measurements of pGlu-His uptake had
a similar effect, causing a significant decrease in the Vmax but not
the Km of transport. The addition of 5 mM magnesium to the uptake
medium prevented the in vitro but not the in vivo effect. The data
indicate that high doses of gentamicin inhibit the capacity but not
the affinity of dipeptide transport in the kidney, prior to
morphological changes which typify acute tubular necrosis. The in
vitro effect is rapid and involves a direct action of gentamicin on
the brush border membrane. The in vivo experiments show that toxicity
may be prolonged, and remains following removal of the drug from the
renal brush border.
Received 15 August 1994; accepted in final form 22 August 1995.
APS Manuscript Number F295-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.