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BioAssay: AID 681878

TP_TRANSPORTER: inhibition of cGMP uptake (cGAMP: 1 uM, cAMP: 250 uM) in membrane vesicles from MRP4-expressing Sf9 cells

The cyclic nucleotides cAMP and cGMP play key roles in cellular signaling and the extracellular regulation of fluid balance. In the kidney, cAMP is excreted across the apical proximal tubular membrane into urine, where it reduces phosphate reabsorption through a dipyridamole-sensitive mechanism that is not fully understood. It has long been known that this cAMP efflux pathway is dependent on ATP more ..
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AID: 681878
Data Source: ChEMBL (839017)
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: The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP.

Abstract: The cyclic nucleotides cAMP and cGMP play key roles in cellular signaling and the extracellular regulation of fluid balance. In the kidney, cAMP is excreted across the apical proximal tubular membrane into urine, where it reduces phosphate reabsorption through a dipyridamole-sensitive mechanism that is not fully understood. It has long been known that this cAMP efflux pathway is dependent on ATP and is inhibited by probenecid. However, its identity and whether cGMP shares the same transporter have not been established. Here the expression, localization, and functional properties of human multidrug resistance protein 4 (MRP4) are reported. MRP4 is localized to the proximal tubule apical membrane of human kidney, and membrane vesicles from Sf9 cells expressing human MRP4 exhibit ATP-dependent transport of [(3)H]cAMP and [(3)H]cGMP. Both probenecid and dipyridamole are potent MRP4 inhibitors. ATP-dependent [(3)H]methotrexate and [(3)H]estradiol-17beta-D-glucuronide transport by MRP4 and interactions with the anionic conjugates S-(2,4-dinitrophenyl)-glutathione, N-acetyl-(2,4-dinitrophenyl)-cysteine, alpha-naphthyl-beta-D-glucuronide, and p-nitrophenyl-beta-D-glucuronide are also demonstrated. In kidneys of rats deficient in the apical anionic conjugate efflux pump Mrp2, Mrp4 expression is maintained at the same level. It is concluded that MRP4 is a novel apical organic anion transporter and the putative efflux pump for cAMP and cGMP in human kidney proximal tubules.
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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