Enhancement of tobramycin binding to rat renal brush border membrane by vancomycin.
Effects of vancomycin (VCM) on tobramycin (TOB) binding to rat renal brush border membrane were examined by using isolated brush border membrane vesicles. The binding of TOB to the membrane vesicle was enhanced by the preincubation of the vesicle with VCM. The Scatchard analysis showed that this enhancement was due mainly to the increase in the number of binding sites. D-Glucose uptake was not affected by VCM, which suggests that the vesicles were not damaged by VCM. The binding of spermine, a typical polycationic compound, to the membrane vesicles also was increased by VCM treatment, and this also was because of the increase in the number of binding sites. These results suggested that the enhanced binding of these cationic compounds by VCM was due to the change in the negative charge on the membrane surface. Considering that the binding of aminoglycosides to brush border membranes is the initial step for the renal accumulation followed by the aminoglycosides-induced nephrotoxicity, this enhancement of TOB binding to the membrane by VCM may be one of the reasons for the enhanced TOB nephrotoxicity by VCM, which has often been reported in experimental animals and patients.
Yano
Y
Y
Shionogi Research Laboratories, Shionogi & CO., LTD., Osaka, Japan.
Hiraoka
A
A
Oguma
T
T
D000818:Animals; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000378:metabolism; D014031:Tobramycin / Q000378:metabolism* / Q000633:toxicity; D014640:Vancomycin / Q000494:pharmacology*
D013096:Spermine; D014640:Vancomycin; D005947:Glucose; D014031:Tobramycin