Interactions between renal brush border membranes and polyamines

BB Kirschbaum

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.

Volume 229, Issue 2, pp. 409-416, 05/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

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