Effect of morphine on P-glycoprotein expression in mouse brain microvascular endothelial cells

Abstract

Objective To investigate the effect of morphine on P-glycoprotein (P-gp) expression in mouse brain microvascular endothelial cells. Methods The mouse brain microvascular endothelial cell line b. End3 was purchased from ATCC company (USA) and cultured at 37 ℃ in high glucose serum-free medium RPMI 1640 in 10 cm petri dishes and assigned to one of 3 groups(n = 9 each): Ⅰ control group (group C); Ⅱ morphine group (group M) and Ⅲ PDTC + morphine group (group P + M). In group M the cells were exposed to morphine 1 μg/ml while in group P + M the cells were pre-incubated with PDTC (NF-κB inhibitor) 5 μmol/L for 1 h before treatment with morphine. In group M and P+ M after being treated with morphine 1 μg/ml for 24 h, the cells were collected for determination of P-gp expression and NF-κB p65-abcb1b protein-DNA binding analysis. Results P-gP expression and NF-κB p65-abcb1b protein-DNA binding were up-regulated in group M as compared with group C. The up-regulation was negated by pre-incubation with PDTC in group P + M. Conclusion Morphine can induce up-regulation of the expression of endogenous P-gp in mouse brain microvascular endothelial cells by NF-κB mediated-abcb1 b gene activation. Key words: Morphine; Endothelium, vascular; Glycoproteins