P-GLYCOPROTEIN AND MULTIDRUG-RESISTANCE

Although the phenomenon of simultaneous resistance to multiple cytotox ic drugs (multidrug resistance) in cancer cells has been discussed for more than two decades, and the human and mouse genes encoding an ener gy-dependent transporter (the multidrug transporter or P-glycoprotein) responsible for multidrug resistance were cloned 10 years ago, there is still considerable controversy about the mechanism of action of thi s efflux pump and its true biological function. This review summarizes the current research on the mechanism of action of the multidrug tran sporter, including the hydrophobic cleaner and altered partitioning mo dels, the possible function of P-glycoprotein as a chloride and/or ATP channel, the role of phosphorylation in its function and fact and spe culation about its physiological role.