Molecular Cloning and Functional Characterization of Cynomolgus Monkey Multidrug Resistance-Associated Protein 2 (MRP2)

Eur J Pharm Sci. 2008 Nov 15;35(4):326-34. doi: 10.1016/j.ejps.2008.08.001. Epub 2008 Aug 9.

Abstract

The monkey is an important experimental model in the pharmacological evaluation of new drugs. We isolated monkey multidrug resistance-associated protein 2 (MRP2) cDNA to examine expression profiles among various tissues and measured ATPase activity to assess substrate specificity. The amino acid sequence encoded by monkey MRP2 cDNA was very similar (96% identity) to the reported human MRP2 cDNA (GenBank accession no. NM_000392). The tissue distribution of MRP2 in monkeys was partially different from that in humans. We found relatively high expression of MRP2 in the monkey kidney and small intestine using Northern blotting. Substrate specificity was compared between human and monkey MRP2. The affinity of 17beta-estradiol 17-(beta-d-glucuronide), methotrexate, vinblastine, and probenecid to monkey MRP2 was higher than that to human MRP2. Functional and expression differences between human and monkey MRP2 should be incorporated into the evaluation of candidate drugs.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Biological Transport, Active
  • Blotting, Northern
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Macaca fascicularis
  • Molecular Sequence Data
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Multidrug Resistance-Associated Proteins / genetics*

Substances

  • DNA, Complementary
  • Indicators and Reagents
  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 2
  • Adenosine Triphosphatases