Expression of P-glycoprotein and multidrug resistance-associated protein on human brain-microvascular endothelial cells with electromagnetic stimulation

This study investigates the effect of electromagnetic field (EMF) on the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) on human brain-microvascular endothelial cells (HBMECs). A monolayer of HBMECs was cocultured with human astrocytes for developing apical/basolateral membrane properties. The results revealed that an increase in the frequency of an EMF enhanced the endocytotic uptake of calcein-AM. Probenecid demonstrated a stronger inhibition to the efflux pumps than verapamil under the exposure to an EMF. The expressed quantities of P-gp and MRP1 after transcytosis of saquinavir were higher than those of azidothymidine, suggesting that the former induced a stronger drug resistance than the latter. In addition, an EMF with 750 Hz could effectively inhibit the expression of P-gp and MRP1. An appropriate exposure to an EMF can be efficient to deliver antiretroviral drugs into the brain via reducing the expressed efflux transporters on HBMECs. (C) 2011 Elsevier B.V. All rights reserved.