Biliary excretion of phenolphthalein sulfate in rats

Pharmacology. 2003 Aug;68(4):177-82. doi: 10.1159/000070456.


Glucuronide and glutathione conjugates have been reported to be substrates of multidrug resistance protein 2 (Mrp2), whereas sulfates of nonbile acid organic anions have never been reported as substrates of Mrp2. To further examine the substrate specificity of Mrp2, we examined the effects of bile acid sulfates on the biliary excretion of phenolphthalein sulfate in rats. The biliary excretion of phenolphthalein sulfate was markedly delayed in Eisai hyperbilirubinemic rats, an Mrp2-deficient strain, and was markedly inhibited by taurolithocholate-3-sulfate. The biliary excretion of leukotriene C(4) metabolites and sulfobromophthalein was inhibited by phenolphthalein sulfate infusion to some extent. These findings suggest that phenolphthalein sulfate is a unique sulfated nonbile acid organic anion which is a substrate of Mrp2.

Publication types

  • Comparative Study

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Animals
  • Anions / metabolism
  • Bile / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Leukotriene C4 / metabolism
  • Male
  • Phenolphthalein / metabolism
  • Phenolphthalein / pharmacokinetics*
  • Rats
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • Sulfobromophthalein / metabolism
  • Taurolithocholic Acid / analogs & derivatives*
  • Taurolithocholic Acid / pharmacology
  • Time Factors


  • ATP-Binding Cassette Transporters
  • Abcc2 protein, rat
  • Anions
  • Carrier Proteins
  • Sulfobromophthalein
  • taurolithocholic acid 3-sulfate
  • Leukotriene C4
  • Taurolithocholic Acid
  • Phenolphthalein