Liu YH, Di YM, Zhou ZW, Mo SL, Zhou SF
MULTIDRUG RESISTANCE ASSOCIATED PROTEINS AND IMPLICATIONS IN DRUG DEVELOPMENT. [JOURNAL ARTICLE]
Clin Exp Pharmacol Physiol 2009 Jun 29.
1. The multidrug resistance associated proteins (MRPs) belongs to the ATP-binding cassette superfamily (ABCC family) of transporters expressed differentially in the liver, kidney, intestine and blood-brain barrier. Human MRPs contains nine members and transport a structurally diverse array of endo- and xenobiotics and their conjugates. 2. MRP1 is distinguished from MRP2 and MRP3 by its higher affinity for leukotriene C(4). By contrast with MRP1, MRP2 functions in the extrusion of endogenous organic anions such as bilirubin glucuronide and certain anticancer agents. In addition to the transport of glutathione and glucuronate conjugates, MRP3 has the additional capability of mediating the transport of monoanionic bile acids. 3. MRP4 and MRP5 have the facility for mediating the transport of cyclic nucleotides and conferring resistance to certain antiviral and anticancer nucleotide analogs. MRP6, whose hereditary deficiency results in pseudoxanthoma elasticum, can transport glutathione conjugates and the cyclic pentapeptide BQ123. 4. Various MRPs show considerable differences in their tissue distribution, substrate specificity, and proposed physiological function. These proteins play a role in drug disposition and excretion and thus are implicated in drug toxicity and drug interactions. An increased efflux of natural product anticancer drugs and other anticancer agents by MRPs in cancer cells is associated with tumor resistance. 5. A better understanding of the function and regulating mechanism of MRPs can help minimize and avoid drug toxicity, unfavourable drug-drug interactions, and to overcome drug resistance.
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