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Interactions between renal brush border membranes and polyamines.

B B Kirschbaum

    The Journal of Pharmacology and Experimental Therapeutics
    |May 1, 1984
    PubMed
    Summary

    Aminoglycosides like gentamicin can alter kidney cell membranes by binding to anionic phospholipids. This interaction, even at low doses, affects membrane structure and function, potentially explaining kidney damage.

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    Area of Science:

    • Nephrology
    • Biochemistry
    • Pharmacology

    Background:

    • Aminoglycosides accumulate in the renal cortex, causing tubular damage.
    • The precise mechanism of aminoglycoside-induced nephrotoxicity at the membrane level requires further elucidation.

    Purpose of the Study:

    • To investigate the interaction characteristics between aminoglycosides and kidney brush border membranes.
    • To understand how aminoglycosides affect membrane structure and function.

    Main Methods:

    • Assay of isolated kidney brush border membrane aggregation induced by gentamicin and netilmicin.
    • Fluorescence analysis using 8-anilino-1-naphthalene sulfonic acid to assess membrane changes.
    • Competition assays with other drugs and spermine to identify interaction sites.

    Main Results:

    • Aminoglycosides induced aggregation of isolated kidney brush border membranes.
    • Competition observed between aminoglycosides and Ca++ or drugs causing phospholipidosis.
    • Gentamicin, even at sub-therapeutic levels, enhanced 8-anilino-1-naphthalene sulfonic acid fluorescence, indicating membrane perturbation.
    • Effects of gentamicin and Ca++ on fluorescence were additive.

    Conclusions:

    • Aminoglycosides directly interact with and modify kidney brush border membrane structure.
    • These interactions involve anionic phospholipids and may be influenced by native polyamines.
    • Subtoxic levels of aminoglycosides can alter membrane characteristics, warranting further investigation into physiological consequences.

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