| MRP3 (ABCC3) is a membrane bound ATP binding cassette (ABC) transporter of the multidrug resistance associated protein subfamily that functions as a key efflux pump for a broad spectrum of organic anions and conjugated xenobiotics across polarized epithelia. It localizes predominantly to the basolateral plasma membrane of hepatocytes, enterocytes, renal tubular cells, and adrenal epithelia, where it couples ATP hydrolysis to the outward transport of compounds such as monoanionic bile acids, glucuronidated and sulfated metabolites, and chemotherapeutic agents including etoposide and paclitaxel, thereby preventing intracellular accumulation and contributing to cellular detoxification and barrier function. In the liver, MRP3 mediated basolateral efflux of bile acid conjugates and drug metabolites into the sinusoidal blood supports cholehepatic and enterohepatic circulation, and its induction during cholestasis serves as an adaptive mechanism to relieve biliary obstruction related toxicity by shunting bile anions into the systemic circulation for renal excretion, while in the intestine MRP3 modulates the net absorption and systemic exposure of orally administered drugs and endogenous anions. MRP3 expression is transcriptionally regulated by nuclear receptors such as PXR, CAR, and FXR, as well as by pro inflammatory and cholestatic signaling cascades, and its upregulation in Dubin Johnson syndrome, where MRP2 is defective, underscores a compensatory role in maintaining bile salt and conjugate efflux in the absence of functional canalicular export. Elevated MRP3 levels are observed in hepatocellular carcinomas, ovarian malignancies, and acute leukemias, where it contributes to chemoresistance by reducing intracellular drug concentrations and is associated with poorer prognosis in adult acute lymphoblastic and myeloid leukemias. |
Lane 1: Human liver, Lane 2: Mouse liver, Lane 3: Rat liver
