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BioAssay: AID 681923

TP_TRANSPORTER: inhibition of E217betaG uptake (E217betaG: 1 uM, cAMP: 300 uM) in membrane vesicles from MRP4-expressing Sf9 cells

Human multidrug resistance protein 4 (MRP4) has recently been determined to confer resistance to the antiviral purine analog 9-(2-phosphonylmethoxyethyl)adenine and methotrexate. However, neither its substrate selectivity nor physiological functions have been determined. Here we report the results of investigations of the in vitro transport properties of MRP4 using membrane vesicles prepared from more ..
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AID: 681923
Data Source: ChEMBL (839062)
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-08-26

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Multidrug resistance-associated protein 4; AltName: Full=ATP-binding cassette sub-family C member 4; AltName: Full=MRP/cMOAT-related ABC transporter; AltName: Full=Multi-specific organic anion transporter B; Short=MOAT-B
Description ..   
Protein Family: ATP-binding cassette domain 2 of multidrug resistance-associated protein
Comment ..   

Gene:ABCC4     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine.

Abstract: Human multidrug resistance protein 4 (MRP4) has recently been determined to confer resistance to the antiviral purine analog 9-(2-phosphonylmethoxyethyl)adenine and methotrexate. However, neither its substrate selectivity nor physiological functions have been determined. Here we report the results of investigations of the in vitro transport properties of MRP4 using membrane vesicles prepared from insect cells infected with MRP4 baculovirus. It is shown that expression of MRP4 is specifically associated with the MgATP-dependent transport of cGMP, cAMP, and estradiol 17-beta-D-glucuronide (E(2)17 beta G). cGMP, cAMP, and E(2)17 beta G are transported with K(m) and V(max) values of 9.7 +/- 2.3 microm and 2.0 +/- 0.3 pmol/mg/min, 44.5 +/- 5.8 microm and 4.1 +/- 0.4 pmol/mg/min, and 30.3 +/- 6.2 microm and 102 +/- 16 pmol/mg/min, respectively. Consistent with its ability to transport cyclic nucleotides, it is demonstrated that the MRP4 drug resistance profile extends to 6-mercaptopurine and 6-thioguanine, two anticancer purine analogs that are converted in the cell to nucleotide analogs. On the basis of its capacity to transport cyclic nucleotides and E(2)17 beta G, it is concluded that MRP4 may influence diverse cellular processes regulated by cAMP and cGMP and that its substrate range is distinct from that of any other characterized MRP family member.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Functional
Target Type: Target is a single protein chain
Assay Data Source: TP-search Transporter Database
Assay Cell Type: Sf9
Assay Test Type: In vitro
Assay Subcellular Fraction: membrane vesicle
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)
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