title: Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways.
abstract: Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as a clinically important antibiotic class because of their reliable efficacy and low cost. However, the clinical use of aminoglycosides is limited by their nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot of studies on characterization of the renal transport system for aminoglycosides so far reported involved various in-vivo and in-vitro techniques. Early studies revealed that aminoglycosides are taken up through adsorptive endocytosis in renal epithelial cells. Subsequently, it was found that megalin, a multiligand endocytic receptor abundantly expressed on the apical side of renal proximal tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin has been suggested to be a promising molecular target for the prevention of aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports have indicated that aminoglycosides are transported via a pathway that does not require endocytosis, such as non-selective cation channel-mediated entry, in cultured renal tubular cells as well as cochlear outer hair cells. In this commentary article, we review the cellular transport of aminoglycosides in renal epithelial cells, focusing on endocytosis-dependent and -independent pathways.
authors.affiliation: Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Nagai
authors.affiliation: Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address: takanom@hiroshima-u.ac.jp.
authors.forename: Mikihisa
authors.initials: M
authors.lastname: Takano
mesh_terms: D000617:Aminoglycosides / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002240:Carbohydrate Sequence; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents
keywords: Amikacin (PubChem CID: 37768); Aminoglycoside antibiotics; Cation channels; Endocytosis; Furosemide (PubChem CID: 3440); Gadolinium (PubChem CID: 23982); Gentamicin (PubChem CID: 3467); Iodo-resiniferatoxin (PubChem CID: 6324614); Megalin; N-methylnicotineamide (PubChem CID: 64950); Netilmicin (PubChem CID: 441306); Renal tubular cells; Resiniferatoxin (PubChem CID: 104826); Streptomycin (PubChem CID: 5999); Tobramycin (PubChem CID: 36294)