Williams P D, Bennett D B, Gleason C R, Hottendorf G H
Antimicrob Agents Chemother. 1987 Apr;31(4):570-4. doi: 10.1128/AAC.31.4.570.
The kinetics of aminoglycoside binding to renal brush border and basolateral membrane vesicles from rat renal cortex were studied by using [3H]amikacin. [3H]amikacin binding to renal membranes was found to be a rapid, saturable process with a fourfold greater affinity for basolateral membranes than for brush border membranes (Kd basolateral = 607 microM; Kd brush border = 2,535 microM). Renal membranes prepared from immature rats (2 to 3 weeks old) exhibited a significantly lower affinity compared with membranes from adults (Kd basolateral = 2,262 microM; Kd brush border = 6,216 microM). Additionally, the inhibitory behavior of several aminoglycosides versus [3H]amikacin binding to brush border membranes revealed the following rank order of potency: neomycin greater than tobramycin approximately gentamicin approximately netilmicin greater than amikacin approximately neamine greater than streptomycin. The relative insensitivity of immature rats to aminoglycoside-induced nephrotoxicity in vivo and the comparative nephrotoxicity of the various aminoglycosides suggest that renal membrane-binding affinity is closely correlated to the nephrotoxic potential of these antibiotics.
利用[³H]阿米卡星研究了氨基糖苷类与大鼠肾皮质肾刷状缘和基底外侧膜囊泡结合的动力学。发现[³H]阿米卡星与肾膜的结合是一个快速、可饱和的过程，对基底外侧膜的亲和力比对刷状缘膜高四倍（基底外侧膜的解离常数Kd = 607微摩尔；刷状缘膜的解离常数Kd = 2535微摩尔）。与成年大鼠的肾膜相比，未成熟大鼠（2至3周龄）制备的肾膜表现出显著更低的亲和力（基底外侧膜的解离常数Kd = 2262微摩尔；刷状缘膜的解离常数Kd = 6216微摩尔）。此外，几种氨基糖苷类对[³H]阿米卡星与刷状缘膜结合的抑制行为显示出以下效力顺序：新霉素大于妥布霉素约等于庆大霉素约等于奈替米星大于阿米卡星约等于新霉素大于链霉素。未成熟大鼠在体内对氨基糖苷类诱导的肾毒性相对不敏感以及各种氨基糖苷类的比较肾毒性表明，肾膜结合亲和力与这些抗生素的肾毒性潜力密切相关。
