Amphotericin B-induced changes in renal membrane permeation: a model of nephrotoxicity.
As part of an investigation into the nephrotoxic effects of the polyene antibiotic Amphotericin B we have studied its effects on the ion permeability of purified renal brush border membrane vesicles. Membrane potentials were measured using a potential sensitive carbocyanine dye, and ion permeabilities were calculated from the constant field equation. Amphotericin B significantly altered the ionic permeability sequence of isolated membranes and caused a selectivity for increasing the permeation of anions. Permeability changes induced by 2.0 micrograms/ml Amphotericin B resulted in an estimated hyperpolarization of the membrane from -50 mV to -72 mV. In addition, the kinetic parameters of Na+ dependent transport of organic metabolites were examined. The maximum change in fluorescence was decreased significantly in the presence of Amphotericin B. These results suggest that the ionic state of the renal cell membrane is significantly altered by the presence of Amphotericin B.
Schell
R E
RE
Department of Oral and Maxillofacial Surgery, Harbor UCLA General Hospital, Torrance 90509.
Tran
N V
NV
Bramhall
J S
JS
D000666:Amphotericin B / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D011817:Rabbits
D009004:Monosaccharide Transport Proteins; D000666:Amphotericin B