Kirschbaum B B
J Pharmacol Exp Ther. 1984 May;229(2):409-16.
Aminoglycosides are cationic polyamines which accumulate in renal cortex and cause functional as well as structural tubular lesions. To examine the characteristics of aminoglycoside interaction with the kidney brush border membrane, we have measured the aggregation of isolated membranes induced by clinically achievable concentrations of gentamicin and netilmicin. In this assay, competition was observed between the aminoglycoside and other drugs which share the property of inducing a phospholipidosis of lysosomes or displacing Ca++ from anionic phospholipids. Competition for aggregation was demonstrated also between gentamicin and spermine which is a native polyamine product of cell metabolism. Additional data supporting a direct effect of the aminoglycosides on membrane structure came from fluorescence analysis utilizing 8-anilino-1-naphthalene sulfonic acid. Concentrations of gentamicin well below therapeutic levels enhanced the fluorescence intensity of 8-anilino-1-naphthalene sulfonic acid several-fold as did low concentrations of Ca++ and Mg++. The effects of gentamicin and Ca++ on 8-anilino-1-naphthalene sulfonic acid fluorescence were additive. These results indicate that membrane characteristics may be modified by the interaction of native polyamines or subtoxic levels of extrinsic polycations with intrinsic anions on the renal cell surface. The physiologic consequences of these changes warrant further study.
氨基糖苷类是阳离子多胺，它们积聚在肾皮质中，导致功能性和结构性肾小管损伤。为了研究氨基糖苷类与肾刷状缘膜相互作用的特征，我们测量了临床可达到浓度的庆大霉素和奈替米星诱导的分离膜的聚集。在该测定中，观察到氨基糖苷类与其他具有诱导溶酶体磷脂沉着症或从阴离子磷脂中置换Ca++特性的药物之间存在竞争。庆大霉素和精胺（一种细胞代谢的天然多胺产物）之间也证明了聚集竞争。利用8-苯胺基-1-萘磺酸进行的荧光分析得出了支持氨基糖苷类对膜结构有直接作用的额外数据。远低于治疗水平的庆大霉素浓度使8-苯胺基-1-萘磺酸的荧光强度增强了几倍，低浓度的Ca++和Mg++也有同样效果。庆大霉素和Ca++对8-苯胺基-1-萘磺酸荧光的作用是相加的。这些结果表明，天然多胺或外源性多阳离子的亚毒性水平与肾细胞表面的内在阴离子相互作用可能会改变膜的特性。这些变化的生理后果值得进一步研究。
