The present study examined how the multidrug resistance protein (MRP) 2, which is an ATP-dependent anionic conjugate transporter, also mediates transport of the chemotherapeutic cationic drug vinblastine (VBL). We show that ATP-dependent [(3)H]VBL (0.2 microM) uptake into membrane vesicles from Sf9 cells infected with a baculovirus encoding rabbit Mrp2 (Sf9-Mrp2) was similar to vesicles from mo...

p-Aminohippurate (PAH) is widely used as a model substrate to characterize organic anion transport in kidney proximal tubules. The carrier responsible for uptake of PAH across the basolateral membrane has been cloned and well characterized, whereas transporters mediating PAH excretion across the brush-border (apical) membrane are yet unknown. In this study we investigated whether PAH is a subst...

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. The transition from chemotherapy-responsive breast cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistance-associated proteins (MRPs). In this study, it was found that TAM-resistant MCF-7 (TAMR-MCF-7) cells expressed higher leve...

The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein/multidrug resistance (MDR) 1 and MDR protein (MRP) 1, is often up-regulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. Five human MRP subfamily members (MRP2-6) with structural similarities to MRP1 have been identified. The relationships between MRP2-...

The expression of multidrug resistance-associated protein isoform 2 (mrp2), the ATP-dependent export pump that mediates the transport of glucuronic acid-, glutathione-, and sulfate-conjugated derivatives, was studied in rat small intestine. The small intestine was divided into nine equal segments, and mrp2 content was analyzed in homogenate and brush border membrane preparations by Western anal...

In renal proximal tubule, multidrug resistance protein 2 (Mrp2) actively transports many organic anions into urine, including drugs and metabolic wastes. Upon exposure to nephrotoxicants or during endotoxemia, both Mrp2 activity and expression are up-regulated. This may result from induced de novo synthesis of Mrp2 or post-transcriptional events involving specific signaling pathways. Here, we i...

A quantitative positron emission tomography (PET) methodology was developed for in vivo kinetic analysis of hepatobiliary transport. Serial abdominal PET scans were performed on normal and multidrug resistance-associated protein 2 (Mrp2)-deficient rats after intravenous injection of (15R)-16-m-[C]tolyl17,18,19,20-tetranorisocarbacyclin methyl ester (15R-[C] TIC-Me) as a radiotracer. 15R-[C]TIC-...

Combined administration of methotrexate (MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs) can result in a decreased systemic clearance of MTX. To date, inhibition of renal uptake via organic anion transporters and efflux via multidrug resistance-associated protein (MRPs) by NSAIDs has been recognized as possible sites of drug interaction between MTX and NSAIDs. Although most NSAIDs are gl...

The multidrug resistance protein MRP1 and its isoform MRP2 are involved in ATP-dependent glutathione S-conjugate transport and have similar substrate specificities. MRP2 mediates hepatic organic anion transport into bile. The physiological function of MRP1 in hepatocytes is unknown. Previous results show that MRP1 expression is low in quiescent hepatocytes but increased after SV40 large T antig...

Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory diseases as well as malignancies. Especially at high MTX dosages, severe adverse effects with this combination may occur, usually resulting from an impaired renal elimination. It has been shown that the mechanism of this interaction cannot be fully attributed to in...