OBJECTIVETo observe the effects of morphine and pethidine on P-glycoprotein (P-gp) expression in mouse brain microvascular endothelial cells and investigate the role of nuclear factor-kappaB (NF-kappaB) signaling pathway in morphine-induced up-expression of P-gp.

METHODSThe mouse brain microvascular endothelial cell line (b.END3) was subjected to pre-incubation with NF-kappaB inhibitor PDTC (5 micromol/L) for 1 h followed by stimulation with morphine (1 microg/ml) or pethidine (1 microg/ml) for 24 h. The bEnd.3 cells were then collected for Western blotting for P-gp expression.

RESULTSA 24-h morphine stimulation induced an up-expression of P-gp in bEnd.3 cells by almost 200%. Pethidine in similar conditions did not affect P-gp expression in the cells. PDTC, the specific inhibitor of NF-kappaB, inhibited morphine-induced up-expression of P-gp in the cells.

CONCLUSIONMorphine can induce up-expression of endogenous P-gp in mouse brain microvascular endothelial cells. NF-kappaB signaling pathway is involved in the morphine-induced up-expression of P-gp.