The multidrug resistance-associated protein (MRP) is the product of an ATP-binding cassette transporter gene overexpressed in some tumor cells resistant to antineoplastic agents. We studied transport function MRP membrane vesicles prepared from HeLa transfected with expression vector and overexpressing this 190-kDa glycoprotein. ATP-dependent primary-active into was demonstrated for leukotriene C4 (LTC4), LTD4, LTE4, S-(2,4-dinitrophenyl)glutathione relative rates, at a substrate...

The multidrug resistance protein MRP1 functions as an ATP-dependent conjugate export pump and confers resistance. We cloned MRP2 (symbol ABCC2), a MRP family member localized to the apical membrane of polarized cells. Stable expression in transfected human embryonic kidney (HEK-293) Madin-Darby canine (MDCK) cells was enhanced by inhibitors histone deacetylase. In MDCK cells, both rat were sorted plasma membrane. An antibody raised against amino terminus recognized recombinant on surface...

ATP-dependent transport of glutathione and glucuronate conjugates from hepatocytes into bile is mediated by a distinct member the ATP-binding cassette superfamily. We have cloned sequenced canalicular isoform multidrug resistance protein rat liver, termed it cMrp. This membrane glycoprotein composed 1541 amino acids with an identity 47.8% human (MRP) 41.9% yeast cadmium factor (YCF1). The carboxyl-terminal 130 hepatocyte MRP (cMRP) were 80.2% identical cMrp.cMrp was not expressed in liver...

We cloned and expressed a new organic anion transporting polypeptide (OATP), termed human OATP2, (OATP-C, LST-1; symbol SLC21A6), involved in the uptake of various lipophilic anions into liver. The cDNA encoding OATP2 comprised 2073 base pairs, corresponding to protein 691 amino acids, which were 44% identical known OATP. An antibody directed against carboxy terminus localized basolateral membrane hepatocytes. Northern blot analysis indicated strong expression only Transport mediated by...

Based on sequence homology to the human organic anion transporting polypeptide 2 (OATP2; SLC21A6), we cloned a new member of SLC21A superfamily solute carriers, termed OATP8 (SLC21A8). The protein 702 amino acids showed an acid identity 80% with OATP2. Northern blotting, expression was restricted liver. Cosmid clones containing genes encoding OATP1 (SLC21A3), OATP2 (SLC21A6), and (SLC21A8) served establish their genomic organization. All three contained 14 exons 13 identical splice sites...

Bilirubin, the end product of heme catabolism, is taken up from blood circulation into liver. This work identifies a high-affinity transport protein mediating uptake bilirubin and its conjugates human hepatocytes. Human embryonic kidney cells (HEK293) permanently expressing recombinant organic anion-transporting polypeptide 2 (human OATP2, also known as LST-1 or OATP-C; symbol SLC21A6) showed [3H]monoglucuronosyl bilirubin, [3H]bisglucuronosyl [3H]sulfobromophthalein withKm values 0.10,...

Background & Aims: The excretion of various organic isoform the multidrug resistance protein (Mrp2). 5,6 anions into bile is mediated by an adenosine triphos-Mrp2 characterized functionally absence canaphate-dependent conjugate export pump, which has licular transport activity for (e.g., been identified as canalicular multiconjugated bilirubin, glutathione (GSH) conjugates, oxidrug (Mrp2).Mrp2 function imdized glutathione, cysteinyl-leukotrienes, acid sulpaired in experimental models...

Several members of the multidrug resistance protein (MRP) family are expressed in liver. Adenosine triphosphate (ATP)-dependent transport glutathione and glucuronoside conjugates across hepatocyte canalicular membrane is mediated by apical MRP isoform, MRP2 (APMRP), also known as multispecific organic anion transporter (cMOAT). We have cloned an additional MRP3, from human liver localized it to basolateral domain hepatocytes. Basolateral (BLMRP) composed 1,527 amino acids encoded 4,581 base...

Cellular export of cyclic nucleotides has been observed in various tissues and may represent an elimination pathway for these signaling molecules, addition to degradation by phosphodiesterases. In the present study we provide evidence that this is mediated multidrug resistance protein isoform MRP5 (gene symbol ABCC5). The transport function was studied V79 hamster lung fibroblasts transfected with a human <i>MRP5</i> cDNA. An MRP5-specific antibody detected overexpression glycoprotein 185 ±...

An important function of hepatocytes is the biotransformation and elimination various drugs, many which are organic cations taken up by cation transporters (OCTs) solute carrier family 22 (SLC22). Because interindividual variability OCT expression may affect response to cationic drugs such as metformin, we systematically investigated genetic nongenetic factors OCT1/SLC22A1 OCT3/SLC22A3 in human liver. OCT1 OCT3 (messenger RNA [mRNA], protein) was analyzed liver tissue samples from 150...

Injection of D-galactosamine sensitizes mice many thousand-fold to the lethal action endotoxin (lipopolysaccharide [LPS]). Comparable sensitization was practically absent in LPS-resistant C3H/HeJ mice, which after treatment were about 500,000 times less sensitive LPS lethality than histocompatible LPS-sensitive C3H/HeN mice. D-Galactosamine induces changes hepatocytes treated animals, such as depletion UTP and alterations pattern UDP sugars. These early biochemical changes, are necessary for...

The effects of d ‐galactosamine, ‐glucosamine, and 2‐deoxy‐ ‐galactose on rat liver uracil nucleotides were studied in vivo . Enzymic isotope dilution analyses the UDP‐sugars uridine phosphates revealed three major, related changes: an accumulation respective UDP‐sugar derivatives, a marked decrease UTP, UDP, UMP, subsequent increase sum hepatic nucleotides. was accompanied by diminished contents UDPG UDP‐galactose. UMP total RNA not altered significantly. Inhibition uridylate synthesis use...

The Dubin-Johnson syndrome is characterized by an inherited defect in the secretion of amphiphilic anionic conjugates from hepatocytes into bile. We have recently identified membrane protein mediating adenosine triphosphate (ATP)-dependent transport glutathione and glucuronate as a multidrug-resistance (MRP) localized it to canalicular well lateral hepatocyte plasma membrane. In present study we show selective absence isoform MRP (cMRP) patient with double-label immunofluorescence confocal...