Inhibition of the enzymatic activity of ligandin by organogermanium, organolead or organotin compounds and the biliary excretion of sulfobromophthalein by the rat

J Pharmacol Exp Ther. 1979 Feb;208(2):248-53.

Abstract

Ligandin binds several classes of compounds, has glutathione-S-transferase activity and is postulated to function in the intracellular transport of substances which bind to it and/or are substrates for its enzymatic activity. The effects of a group of organometals reported to inhibit the enzymatic activity of ligandin on the biliary excretion of sulfobromophthalein have been investigated to determine what role the enzymatic activity of ligandin has with respect to the biliary excretion of the dye. Triethyllead reduced the rate of dye excretion into the bile without affecting blood pressure, blood or liver sulfhydryl compounds or the volume of bile flow. The organometal had no effect on the initial rate of plasma dye clearance. Inhibited biliary sulfobromophthalein excretion by triethylead-treated rats correlated with relative increases in liver and bile unconjugated dye, decreases in liver and bile conjugated dye and reduced glutathione-S-aryltransferase activity in supernatant fractions isolated from the liver. The results clearly demonstrated that the tested organometals can inhibit the enzymatic activity of ligandin in vivo and suggested that, if ligandin has a role in the translocation of the dye from the blood to the liver, the enzymatic activity of the protein may not be involved.

MeSH terms

  • Animals
  • Bile / drug effects
  • Bile / metabolism*
  • Germanium / pharmacology*
  • Glutathione Transferase / antagonists & inhibitors*
  • Lead / pharmacology*
  • Male
  • Organometallic Compounds / pharmacology*
  • Organotin Compounds / pharmacology*
  • Rats
  • Sulfobromophthalein / blood
  • Sulfobromophthalein / metabolism
  • Time Factors
  • Triethyltin Compounds / pharmacology

Substances

  • Organometallic Compounds
  • Organotin Compounds
  • Triethyltin Compounds
  • Germanium
  • Sulfobromophthalein
  • Lead
  • Glutathione Transferase