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BioAssay: AID 681870

TP_TRANSPORTER: inhibition of alaninyl-d4TMP by Thromboxane B2 at a concentration of 20uM in membrane vesicle from MRP5-expressing HEK293 cells

Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have investigated the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter more ..
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 Tested Compounds
 Tested Compounds
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Unspecified(1)
 
 
 Tested Substances
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 Related BioAssays
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AID: 681870
Data Source: ChEMBL (839009)
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-05-27

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Multidrug resistance-associated protein 5; AltName: Full=ATP-binding cassette sub-family C member 5; AltName: Full=Multi-specific organic anion transporter C; Short=MOAT-C; AltName: Full=SMRP; AltName: Full=pABC11
Description ..   
Protein Family: ATP-binding cassette domain 2 of multidrug resistance-associated protein
Comment ..   

Gene:ABCC5     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs.

Abstract: Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have investigated the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps. In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2. In contrast, MRP1, MRP2, MRP3, and MRP5 did not transport PGE1 or PGE2. The MRP4-mediated transport of PGE1 and PGE2 displayed saturation kinetics, with Km values of 2.1 and 3.4 microM, respectively. Further studies showed that PGF1alpha, PGF2alpha, PGA1, and thromboxane B2 were high-affinity inhibitors (and therefore presumably substrates) of MRP4. Furthermore, several nonsteroidal antiinflammatory drugs were potent inhibitors of MRP4 at concentrations that did not inhibit MRP1. In cells expressing the prostaglandin transporter PGT, the steady-state accumulation of PGE1 and PGE2 was reduced proportional to MRP4 expression. Inhibition of MRP4 by an MRP4-specific RNA interference construct or by indomethacin reversed this accumulation deficit. Together, these data suggest that MRP4 can release prostaglandins from cells, and that, in addition to inhibiting prostaglandin synthesis, some nonsteroidal antiinflammatory drugs might also act by inhibiting this release.
Categorized Comment
Assay Type: Functional

Assay Data Source: TP-search Transporter Database

Assay Test Type: In vitro

BAO: Assay Format: subcellular format

Assay Cell Type: HEK293

Assay Subcellular Fraction: membrane vesicle

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)
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Classification
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