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INHIBITION OF GENTAMICIN UPTAKE INTO CULTURED MOUSE PROXIMAL TUBULE EPITHELIAL-CELLS BY L-LYSINE
Author(s): KAUNITZ JD, CUMMINS VPS, MISHLER D, NAGAMI GT
Source: JOURNAL OF CLINICAL PHARMACOLOGY    Volume: 33    Issue: 1    Pages: 63-69    Published: JAN 1993  
Times Cited: 13     References: 38     
Abstract: Gentamicin uptake and toxicity was studied in a nontransformed cell line obtained from the Sl 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 mug/mL gentamicin, 0.5 mmol/L L-lysine, or gentamicin plus L-lysine. Uptake of 300 mug/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 mug/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.
Document Type: Article
Language: English
Reprint Address: KAUNITZ, JD (reprint author), UNIV CALIF LOS ANGELES, WADSWORTH VET AFFAIRS MED CTR, DEPT MED, RES SERV, LOS ANGELES, CA 90073 USA
Addresses:
1. UNIV CALIF LOS ANGELES, WADSWORTH VET AFFAIRS MED CTR, DEPT MED, MED SERV, LOS ANGELES, CA 90073 USA
Publisher: LIPPINCOTT-RAVEN PUBL, 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
Subject Category: Pharmacology & Pharmacy
IDS Number: KG670
ISSN: 0091-2700
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