“Our article synthesized the current literature on the rapidly expanding field of ATP-binding cassette transporters involved in cellular export of drugs and toxins.”

This paper was an invited review article in a special issue of the journal Toxicology and Applied Pharmacology on the subject of "Membrane Proteins in Toxicology." Our article synthesized the current literature on the rapidly expanding field of ATP-binding cassette transporters involved in cellular export of drugs and toxins.

The ATP-binding cassette (ABC) transport proteins P-glycoprotein (ABCB1), MRP1 (ABCC1), MRP2 (ABCC2), and BCRP (ABCG2) were the main focus of the article. These ATP-dependent transport proteins protect tissues from a variety of harmful chemicals, including bulky lipophilic cationic, anionic, and neutrally charged drugs and toxins, as well as conjugated organic anions.

Thus, in addition to therapeutic agents, these ABC proteins mediate the transmembrane efflux of dietary and environmental carcinogens, pesticides, metals, metalloids, and lipid peroxidation products. These transporters have an important role in maintaining the barrier function of sanctuary site tissues (e.g., blood-brain barrier, blood-cerebral spinal fluid barrier, blood-testis barrier, and the maternal-fetal barrier or placenta) and are increasingly recognized for their ability to modulate the absorption, distribution, metabolism, and excretion of xenobiotics—hence their efficacy and toxicity.

Thus they are of major interest to toxicologists, pharmacologists, and clinicians in both the academic and pharmaceutical communities. This article focused more on the role of ABC proteins in toxicology than the structure and function/catalytic cycle. The toxicology focus was likely an important reason for its popularity.

An important function of the cells that make up and line our organs (e.g., the liver, kidney, and intestine) is to protect our bodies from daily exposure to environmental toxins and drugs. These protective cells have many proteins on their surface (or membrane) and some of these proteins can prevent harmful chemicals from accumulating in cells by pumping them out. This review summarizes recent work on the properties of four of these energy-dependent membrane proteins and how they protect key organs in the body from toxins (P-glycoprotein, MRP1, MRP2, and BCRP/ABCG2).