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  • Title: Surface binding and intracellular uptake of gentamicin in the cultured kidney epithelial cell line (LLC-PK1).
    Author: Hori R, Okuda M, Ohishi Y, Yasuhara M, Takano M.
    Journal: J Pharmacol Exp Ther; 1992 Jun; 261(3):1200-5. PubMed ID: 1602385.
    Abstract:
    Aminoglycoside antibiotics such as gentamicin are taken up by renal proximal tubular cells, yet little is known regarding the biochemical characteristics of the transport process at the cellular level. In this report, cellular handling of gentamicin was studied in the cultured kidney epithelial cell line LLC-PK1. After 2 days of incubation of the cells with gentamicin, cell-associated gentamicin decreased rapidly during the first 30 min when the cells were incubated in gentamicin-free medium, then decreased slowly. The apparent half-life of the latter phase, which should represent release from the intracellular compartment, was about 2.0 days. The rapid release of gentamicin should consist of two components, one is a release from the cell surface membrane and the other from domes. Cell surface binding of gentamicin was dependent on the ambient ionic strength. The intracellular uptake was inhibited by low temperature, neomycin, metabolic inhibitors and reagents which interact with the cytoskeleton. On the other hand, the uptake was not affected by d-glucose, organic cations and an organic anion. Thus, by estimating the intracellular gentamicin separately from the drug localized in other compartments, it is concluded that gentamicin is taken up by LLC-PK1 cells via an adsorptive endocytosis. The endocytosis of gentamicin should be dependent on metabolic energy and cytoskeletal function.
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