RRC ID 42301
著者 Kimura O, Endo T, Hotta Y, Sakata M.
タイトル Effects of P-glycoprotein inhibitors on transepithelial transport of cadmium in cultured renal epithelial cells, LLC-PK1 and LLC-GA5-COL 150.
ジャーナル Toxicology
Abstract The purpose of this study using LLC-PK(1) cells and P-glycoprotein (P-gp) overexpressed LLC-PK(1) cells (LLC-GA5-COL 150 cells) was to investigate the secretory transport of cadmium (Cd) via endogenous and overexpressed P-gp, respectively. Cell monolayers cultured on permeable membranes were incubated at 37 degrees C for 60 min with 1 microM CdCl(2) from either the apical or the basolateral side. The basolateral-to-apical transport of Cd was 1.7 times higher than the apical-to-basolateral transport of Cd in LLC-GA5-COL 150 cells, while the transport from apical and basolateral sides was almost the same in LLC-PK(1) cells. Treatment with a P-gp monoclonal antibody, UIC2, significantly decreased the basolateral-to-apical transport of Cd in LLC-PK(1) and LLC-GA5-COL 150 cells, and significantly increased the apical-to-basolateral transport of Cd in both cells. The effects of UIC2 were more marked in LLC-GA5-COL 150 cells than in LLC-PK(1) cells. Furthermore, typical P-gp inhibitors such as cyclosporin A, and doxorubicin decreased the basolateral-to-apical transport of Cd slightly in LLC-PK(1) cells and significantly in LLC-GA5-COL 150 cells. These results suggest that Cd is extruded from the apical membrane of LLC-PK(1) and LLC-GA5-COL 150 cells, probably depending on the level of P-gp expression.
巻・号 208(1)
ページ 123-32
公開日 2005-3-1
DOI 10.1016/j.tox.2004.11.015
PII S0300-483X(04)00614-6
PMID 15664439
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors* ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Animals Biological Transport Cadmium / pharmacokinetics* Cadmium Radioisotopes Cell Membrane / metabolism* Doxorubicin / pharmacokinetics Epithelial Cells / drug effects* Epithelial Cells / metabolism LLC-PK1 Cells Organic Cation Transport Proteins / metabolism Protein Biosynthesis Swine
IF 4.099
引用数 16
WOS 分野 PHARMACOLOGY & PHARMACY TOXICOLOGY
リソース情報
ヒト・動物細胞 LLC-GA5-CoL150(RCB0871)