Membrane Transporters and Pharmacological Implications

Membrane transporters serve to move chemicals in and out of the cells according to metabolic needs or the presence of toxic compounds. These processes are mediated by facilitated diffusion or active transport through the lipid bilayer that is the cell membrane. There exist two main categories of membrane transporters, the more passive solute carrier transporters (SLCs) and the ATP binding cassette transporters (ABCs). SLCs allow for passage of ions, sugars, lipids, amino acids and other compounds down a gradient, contributing to a cell’s passive permeability for such compounds. ABCs feature a highly conserved nucleotide binding domain (NBD) which contain peptide sequences responsible for ATP hydrolysis such as the Walker A and B motifs. ABCs utilize the energy stored in ATP to transport chemicals against their concentration and/or electrical gradient and consequently alter expected biological conditions. Transporters are now recognized as crucial barriers (e.g., efflux transporters) as well as possible delivery pathways to consider when designing new pharmaceutical agents as many traditional therapeutics are being recognized as transporter substrates [1–3]. Drug resistant tumors and the blood-brain barrier (BBB) for example have been shown to actively express efflux transporters preventing therapeutic agents from reaching clinically relevant intracellular concentrations and/or physiological targets in the brain [4–7].