INTERACTIONS BETWEEN RENAL BRUSH-BORDER MEMBRANES AND POLYAMINES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (2) , 409-416
Abstract
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 the aggregation of isolated [rat] membranes induced by clinically achievable concentrations of [nephrotoxic antibiotics] gentamicin and netilmicin was measured. In this assay, competition was observed between the aminoglycoside and other drugs which share the property of inducing a phospholipidosis of lysosomes or displacing Ca2+ 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 using 8-anilino-1-napthalene 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 Ca2+ and Mg2+. The effects of gentamicin and Ca2+ on 8-anilino-1-naphthalene sulfonic acid fluorescence were additive. 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.