Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers
The multixenobiotic resistance (MXR) mechanism, mediated by activity of the transmembrane P-glycoprotein, represents a basic biological defence system in aquatic organisms. Here we investigate the MXR transport activity in an aquatic vertebrate, the common carp (Cyprinus carpio). We measured the accumulation rate of a model MXR substrate, the fluorescent dye rhodamine B (RB), in gills, lateral muscles, liver and bile. Results obtained using this method showed a significant increase of RB accumulation in tissues of fish exposed for I h to 3 microM RB in the presence of the model MXR inhibitors cyclosporin A (CA, 5 microM) or verapamil (VER, 10 microM), when compared with specimens exposed without inhibitors. The highest increase in RB accumulation detected in the liver (VER 54%, CA 170%) indicates that among the tissues analysed within this study, liver is the most prominent candidate organ for the functional detection of MXR activity in C. carpio.