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Inhibition of Gentamicin Uptake into Cultured Mouse Proximal Tubule Epithelial Cells by L‐Lysine
Author(s) -
Kaunitz Jonathan D.,
Cummins Vierka P. Smith,
Mishler Delta,
Nagami Glenn T.
Publication year - 1993
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1993.tb03905.x
Subject(s) - gentamicin , lysine , toxicity , aminoglycoside , chemistry , biochemistry , microbiology and biotechnology , biology , amino acid , antibiotics , organic chemistry
Gentamicin uptake and toxicity was studied in a nontransformed cell line obtained from the S1 segment of the proximal tubule epithelium of a transgenic mouse. Cytotoxicity was assayed using the dye 3‐(4,‐5dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT). Gentamicin uptake was assayed by a fluorescence polarization assay. No differences in toxicity were found among cells incubated for 4 hours in complete culture medium, enriched Kreb's buffer alone, or enriched Krebs' buffer with added 300 μg/mL gentamicin, 0.5 mmol/L L‐lysine, or gentamicin plus L‐lysine. Uptake of 300 μg/mL gentamicin was minimal at zero time and increased as a function of time. Uptake of gentamicin at 4 hours was positively correlated with medium gentamicin concentration. Addition of 0.5 mmol/L L‐lysine inhibited uptake of 300 μg/mL gentamicin 38.9 ± 10.2%. No other amino acid, including D‐lysine or arginine, significantly changed gentamicin uptake. The authors conclude that gentamicin and L‐lysine share a specific uptake mechanism located in the apical membrane of renal proximal tubule cells.