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Literature summary for 7.6.2.2 extracted from

  • Bodo, A.; Bakos, E.; Szeri, F.; Varadi, A.; Sarkadi, B.
    The role of multidrug transporters in drug availability, metabolism and toxicity (2003), Toxicol. Lett., 140-141, 133-143.
    View publication on PubMed
Search for more literature for 7.6.2.2

Activating Compound

Activating Compound Comment Organism Structure
benzbromarone slightly activates E217betaG activated ATPase activity of MRP3 at 0.01-0.03 mM, benzbromarone may be a potential transported substrate for MRP3, greatly stimulates E217betaG uptake by MRP3 at 0.001-0.02 mM, but inhibits this activity at 0.05 mM Homo sapiens
glutathione 5 mM free GSH activates the indomethacin transport by MRP1, no effect on the other substrates tested or on MRP3 activity Homo sapiens
MK571 slightly activates E217betaG activated ATPase activity of MRP3 at 0.01-0.05 mM and N-ethylmaleimide S-glutathione activated ATPase activity of MRP1 at 500-2000 nM, but inhibits MRP1 activity half-maximally at 0.01 mM, MK571 may be a potential transported substrate for MRP3, 20% stimulation of E217betaG uptake by MRP1 at 500-1000 nM, but inhibits this activity at 0.01-0.05 mM, stimulates E217betaG uptake by MRP3 at 0.002-0.005 mM, but inhibits this activity at 0.05-0.1 mM Homo sapiens

Application

Application Comment Organism
pharmacology the investigation of the substrate interactions and modulation of multidrug transporters may pave the way for predictive toxicology and pharmacogenomics Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
MRP1 and MRP3, expression in Sf9 cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
benzbromarone 50% inhibition of N-ethylmaleimide S-glutathione activated ATPase activity of MRP1 at 0.01 mM, 50% inhibition of E217betaG uptake by MRP1 at 0.005-0.008 mM, inhibits E217betaG uptake by MRP3 at 0.05 mM, but greatly stimulates this activity at 0.001-0.02 mM Homo sapiens
MK571 50% inhibition of N-ethylmaleimide S-glutathione activated ATPase activity of MRP1 at 0.01 mM, but slightly activates this activity at 500-2000 nM, 100% inhibition of E217betaG uptake by MRP1 at 0.01-0.05 mM, but stimulates this activity at 500-1000 nM, inhibits E217betaG uptake by MRP3 at 0.05-0.1 mM, but stimulates this activity at 0.002-0.005 mM Homo sapiens
vanadate inhibits ATPase activity Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.008 0.01 E217betaG pH 7, 37°C, MRP1 Homo sapiens
0.03 0.035 E217betaG pH 7, 37°C, MRP3 Homo sapiens
0.3
-
 N-ethylmaleimide S-glutathione/in pH 7, 37°C, MRP1 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane
-
 Homo sapiens 16020
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
160000
-
 x * 160000, recombinant MRP1 and MRP3, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O + xenobiotic/in Homo sapiens multidrug resistance, the major physiological role is the protection of cells and tissues against xenobiotics, relevance of MRP1 and MRP3 proteins in chemoresistance of cancer and in drug metabolism and toxicity ADP + phosphate + xenobiotic/out
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O + E217betaG/in MRP3 preferentially transports E217betaG with a medium affinity and a very high capacity, while MRP1 transports E217betaG with a higher affinity but with much lower capacity Homo sapiens ADP + phosphate + E217betaG/out
-
 ?
ATP + H2O + furosemide/in good substrate for MRP3, but not for MRP1 Homo sapiens ADP + phosphate + furosemide/out
-
 ?
ATP + H2O + indomethacin/in moderate substrate for MRP1, weak substrate for MRP3 Homo sapiens ADP + phosphate + indomethacin/out
-
 ?
ATP + H2O + N-ethylmaleimide S-glutathione/in NEM-GS is a good substrate for MRP1, but not for MRP3 Homo sapiens ADP + phosphate + N-ethylmaleimide S-glutathione/out
-
 ?
ATP + H2O + xenobiotic/in multidrug resistance, the major physiological role is the protection of cells and tissues against xenobiotics, relevance of MRP1 and MRP3 proteins in chemoresistance of cancer and in drug metabolism and toxicity Homo sapiens ADP + phosphate + xenobiotic/out
-
 ?
ATP + H2O + xenobiotic/in wide substrate specificity of MDR proteins, MDR1 preferentially extrudes large hydrophobic, positively charged molecules, members of the MRP family extrudes both hydrophobic uncharged molecules and water-soluble anionic compounds Homo sapiens ADP + phosphate + xenobiotic/out
-
 ?
additional information benzbromarone and MK571 may be potential transported substrates for MRP3 Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
? x * 160000, recombinant MRP1 and MRP3, SDS-PAGE Homo sapiens

Synonyms

Synonyms Comment Organism
MDR1 P-glycoprotein Homo sapiens
MRP1 member of the MRP family Homo sapiens
MRP3 member of the MRP family Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
additional information
-
 additional information MRP3 has a lower turnover rate than MRP1 Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
 assay at Homo sapiens