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) |