Electronic Resource
Springer
Naunyn-Schmiedeberg's archives of pharmacology
300 (1977), S. 67-76
ISSN:
1432-1912
Keywords:
Polycations
;
Aminoglycosides
;
Kidney
;
Brush border membrane
;
Lysosomes
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. Experiments with Brush Border Membranes Drugs were screened for inhibition of 125I-aprotinin binding to isolated rat renal brush border membranes. Cationic polymers were effective, and their primary amino groups were crucial. The polycationic aminoglycosides displaced 125I-aprotinin with low concentrations (50% inhibition by 50 μg/ml of gentamicin). The decreasing sequence of both number of amino groups and of inhibitory potency was: neomycin 〉 tobramycin 〉 gentamicin 〉 kanamycin 〉 streptomycin. Binding of 3H-gentamicin-C1 to the brush border membrane was saturable. The Scatchard plot indicated an association constant of 43 mM−1, and 18 nmoles per mg of membrane protein for the number of binding sites. Inhibition of 125I-aprotinin binding by gentamicin was competitive. The inhibition constant (KI) was 20 μg/ml with concentrations of 8 and 40 μg/ml of gentamicin. 2. Experiments with Lysosomes Gentamicin and aprotinin (200 μg/ml) activated β-glucuronidase and β-galactosidase from renal lysosomes, but not acid phosphatase. Gentamicin and aprotinin (300 μg/ml) increased the release of acid phosphatase from intact renal lysosomes. Lysosomal degradation of 125I-aprotinin into acid soluble split products was much slower than that of 125I-insulin. From our present and previous results it is concluded that binding to the brush border membrane occurs with chemically quite different, however basic drugs and that the number of amino groups per molecule is relevant. Nephrotoxicity of aminoglycosides may be related to their endocytic uptake through a direct action on lysosomes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00505081
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