RRC ID 62167
著者 Endo T, Kimura O, Sakata M.
タイトル Effects of P-glycoprotein inhibitors on cadmium accumulation in cultured renal epithelial cells, LLC-PK1, and OK.
ジャーナル Toxicol Appl Pharmacol
Abstract The purpose of this study was to investigate whether cadmium (Cd) efflux across the apical membrane of cultured renal epithelial cells, LLC-PK(1) and OK, is mediated via P-glycoprotein (P-gp). These cells were preincubated for 30 min with a typical P-gp inhibitor such as verapamil, diltiazem, nifedipine, vinblastine, or cyclosporin A before the incubation with 1 microM (109)CdCl(2) for 15 min. Preincubation with each P-gp inhibitor significantly increased Cd accumulation in LLC-PK(1), and OK cells. Treatment of these cells with UIC2, a P-gp monoclonal antibody, also significantly increased Cd accumulation in these cells. Thus, the pretreatment of cells with P-gp inhibitor appears to increase Cd accumulation as a result of the inhibition of Cd efflux via P-gp. To confirm Cd efflux via P-gp, Cd accumulation in P-gp-overexpressed cells (LLC-GA5-COL150 cells) was compared with that in parental LLC-PK(1) cells. LLC-GA5-COL150 cells accumulated less Cd than did LLC-PK(1) cells, and the effects of the P-gp inhibitors and UIC2 on Cd accumulation were greater in LLC-GA5-COL150 cells. These results suggest that P-gp in LLC-PK(1) and OK cells appear to act as an efflux pump of Cd, decreasing cellular Cd accumulation.
巻・号 185(3)
ページ 166-71
公開日 2002-12-15
DOI 10.1006/taap.2002.9533
PII S0041008X02995335
PMID 12498733
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors* Animals Antibodies, Blocking / pharmacology Antibodies, Monoclonal / pharmacology Cadmium / metabolism* Cadmium Radioisotopes Calcium Channel Blockers / pharmacology Cyclosporine / pharmacology Epithelial Cells / drug effects Epithelial Cells / metabolism* Fluorescent Dyes Kidney / drug effects Kidney / metabolism* LLC-PK1 Cells Protein Biosynthesis Rats Rhodamine 123 Swine Vinblastine / pharmacology
IF 3.347
リソース情報
ヒト・動物細胞 LLC-GA5-CoL150(RCB0871)