1α,25-Dihydroxyvitamin D3-liganded vitamin D receptor increases expression and transport activity of P-glycoprotein in isolated rat brain capillaries and human and rat brain microvessel endothelial cells.

ABSTRACT: Induction of the multidrug resistance protein 1 (MDR1)/P-glycoprotein (P-gp) by the vitamin D receptor (VDR) was investigated in isolated rat brain capillaries and rat (RBE4) and human (hCMEC/D3) brain microvessel endothelial cell lines. Incubation of isolated rat brain capillaries with 10 nM of the VDR ligand, 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] for 4 h increased P-gp protein expression fourfold. Incubation with 1,25(OH)(2)D(3) for 4 or 24 h increased P-gp transport activity (specific luminal accumulation of NBD-CSA, the fluorescent P-gp substrate) by 25-30%. In RBE4 cells, Mdr1b mRNA was induced in a concentration-dependent manner by exposure to 1,25(OH)(2)D(3). Concomitantly, P-gp protein expression increased 2.5-fold and was accompanied by a 20-35% reduction in cellular accum

SUBMITTER: Durk MR 

PROVIDER: S-EPMC3538370 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature