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BioAssay: AID 682111

TP_TRANSPORTER: ATP-dependent uptake of cAMP at a concentration of 10 uM in membrane vesicle from MRP8-expressing LLC-PK1 cells

We previously determined that expression of human multidrug resistance protein (MRP) 8, a recently described member of the MRP family of ATP-binding cassette transporters, enhances cellular extrusion of cyclic nucleotides and confers resistance to nucleotide analogs (J Biol Chem 278:29509-29514, 2003). However, the in vitro transport characteristics of the pump have not been determined. In this more ..
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 Tested Compounds
 Tested Compounds
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Unspecified(1)
 
 
 Tested Substances
 Tested Substances
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 Related BioAssays
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AID: 682111
Data Source: ChEMBL (839250)
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2013-11-17

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=ATP-binding cassette sub-family C member 11; AltName: Full=Multidrug resistance-associated protein 8
Description ..   
Protein Family: ATP-binding cassette domain 2 of multidrug resistance-associated protein
Comment ..   

Gene:ABCC11     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11).

Abstract: We previously determined that expression of human multidrug resistance protein (MRP) 8, a recently described member of the MRP family of ATP-binding cassette transporters, enhances cellular extrusion of cyclic nucleotides and confers resistance to nucleotide analogs (J Biol Chem 278:29509-29514, 2003). However, the in vitro transport characteristics of the pump have not been determined. In this study, the substrate selectivity and biochemical activity of MRP8 is investigated using membrane vesicles prepared from LLC-PK1 cells transfected with MRP8 expression vector. Expression of MRP8 is shown to stimulate the ATP-dependent uptake of a range of physiological and synthetic lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate. In addition, MRP8 is competent in the in vitro transport of cAMP and cGMP, in accord with the results of our previously reported cellular studies. DHEAS, E(2)17betaG, and methotrexate were transported with K(m) and V(max) values of 13.0 +/- 0.8 microM and 34.9 +/- 9.5 pmol/mg/min, 62.9 +/- 12 microM and 62.0 +/- 5.2 pmol/mg/min, and 957 +/- 28 microM and 317 +/- 17 pmol/mg/min, respectively. Based upon the stimulatory action of DHEAS on uptake of E(2)17betaG, the attenuation of this effect at high DHEAS concentrations and the lack of reciprocal promotion of DHEAS uptake by E(2)17betaG, a model involving nonreciprocal constructive interactions between some transport substrates is invoked. These results suggest that MRP8 participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides and indicate that the pump has complex interactions with its substrates.
Categorized Comment
ChEMBL Assay Type: Functional

ChEMBL Assay Data Source: TP-search Transporter Database

ChEMBL Assay Test Type: In vitro

ChEMBL Assay Cell Type: LLC-PK1 (Renal epithelial cells)

ChEMBL Assay Subcellular Fraction: membrane vesicle

ChEMBL Target ID: 104643

ChEMBL Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat%
5Activity standard valueActivity standard valueFloat%

Data Table (Concise)
Classification
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