ABC 수송단백과 약물수송

ABC Transporters and Drug Transport

The ATP-binding cassette (ABC) transporters are involved in a variety of biologic processes in human and other organisms. Currently, 49 ABC transporter genes were identified in human genome and classified into 7 subfamilies according to their sequence homologies. The ABC proteins provide nutrients to the cells, protect them from a wide range of toxic compounds, and regulate basic biologic processes of essential organs such as alimentary tract, liver, lung and immune systems. Consequently, mutations affecting ABC-transporters have been found to be the underlying causes for a large number of human inherited diseases and individual diversity of drug responses. For example, aberrant membrane transport caused by mutations in CFTR gene is associated with a wide spectrum of respiratory and digestive diseases as well as cystic fibrosis. A group of ABC genes code the multi-drug resistance (MDR) and multidrug resistance-related proteins (MRPs) , which function as xenobiotic transporters. MDRI was originally identified as a gene that confers multi-drug resistance to cancer cells. The MRPs were discovered as a second type of drug pump in cancer cells exhibiting multi-drug resistance not caused by MDRl. However, recently it was found that they are the native exporters having physiological role of protecting organism from various toxic substances including commonly prescribed medications. Thus, identifying the individual genetic variations of these transporters carries significant meaning in pharmacotherapy of post-genomic era, since such genetic variants are likely to be an important source for the inter-individual variability in pharmacokinetics and pharmacodynamics of many drugs. Future investigations in large scale analysis of ABC transporter genes will provide the basis for understanding the pathogenesis of many genetic disorders and for elucidating the molecular mechanisms related to individual diversity of drug responses.