Transport of thiophenorphine across Caco-2 monolayer model
10.3867/j.issn.1000-3002.2010.01.011
- VernacularTitle:噻吩诺啡在Caco-2细胞上的转运特征
- Author:
Zheng LI
;
Xiaomei ZHUANG
;
Suyun LI
;
Zhenqing ZHANG
;
Jinxiu RUAN
- Publication Type:Journal Article
- Keywords:
thiophenorphine;
chromatography,high pressure liquid;
cells,cultured;
glycoproteins;
multidrug resistance-associated proteins
- From:
Chinese Journal of Pharmacology and Toxicology
2010;24(1):64-68
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the absorption mechanism of thiophenorphine, and its effect on P-glycoprotein (P-gp) expression by using Caco-2 cell monolayer model. METHODSThe LC-MS-MS method was applied to determine thiophenorphine concentration in millicell system. The bi-directional permeability studies were performed to investigate the potential involvement of efflux carriers in the intestinal absorption. P-gp inhibition was studied by flow cytometry using calcein-AM as P-gp substrate.The expression of P-gp was evaluated using Western blotting. RESULTSThiophenorphine transport in Caco-2 cells was in time-dependent manner. Its average apparent permeability coefficient (P_(app)) was 2.338×10~(-6) cm·s~(-1). P_(app) was increased 2.8 folds by P-gp inhibitor ciclosporin A, and 2.3 folds by mulitdrug resistance-associated protein2 (MRP2) inhibitor MK571. The accumulation of calcein-AM and the expression of P-gp in Caco-2 cell line wasn't changed noticeably by thiophenorphine. CONCLUSION Thiophenorphine is a common substrate of P-gp and MRP2 and it shows normal transport in millicell system. The expression of P-gp doesn't induce by thiophenorphine.
