The role of multi-drug resistance p-glycoprotein in glucocorticoid function: Studies in animals and relevance in humans

Entry of glucocorticoid hormones into cells is tightly regulated by membrane transporters. One of these transporters, the multi-drug resistance p-glycoprotein, has been extensively described to confer treatment resistance to tumour cells as well as to regulate the intracellular levels of glucocorticoid hormones. Moreover, multi-drug resistance p-glycoprotein is also present on the endothelial cells of the blood–brain-barrier, and in neurones, where it limits the access of glucocorticoids to the brain. Finally, this transporter also has the ability to limit the entry of some antidepressants to the brain, with potential consequences for the clinical therapeutic effects of these drugs. This review will focus on the studies that have used multi-drug resistance p-glycoprotein knockout animals in such context, and will discuss the potential clinical relevance of these transporters for psychiatric disorders. In particular, we will discuss the reciprocal interactions between this transporter and antidepressants, both as its inhibitors and as its substrates. We believe that the interaction between antidepressants and multi-drug resistance p-glycoprotein is one of the most potentially exciting developments in psychopharmacological research.