gamma-Glutamyltransferase-dependent biliary-hepatic recycling of methyl mercury in the guinea pig.
After secretion into bile, glutathione (GSH) and GSH-conjugates are catabolized by gamma-glutamyltransferase (gamma-GT) and dipeptidases yielding glutamate, cysteine, glycine and cysteine S-conjugates, and these products are then partially reabsorbed from the biliary tree. Because methyl mercury is thought to be secreted into bile as a GSH- complex, it may be subject to a similar intrahepatic cycle, thus delaying its elimination. To examine this possibility guinea pigs were dosed with 203Hg-methyl mercury (10 mumol/kg i.v.), followed by a retrograde intrabiliary infusion of Krebs-Henseleit buffer (control) or acivicin (an inhibitor of gamma-GT). Acivicin increased biliary excretion of 203Hg by 41%, and GSH from 0.14 +/- 0.10 to 2.02 +/- 0.26 nmol/min.g of liver. Bile analyzed by gel filtration chromatography revealed that CH(3)203Hg-GSH accounted for most of this increased 203Hg excretion. When CH(3)203Hg-complexes of GSH, cysteine and albumin were introduced directly into the biliary tree by retrograde infusion, 203Hg recovery in bile was significantly lower than recovery of the nonabsorbable marker [14C]sucrose, ranging from 26.0 +/- 2.9% for CH(3)203Hg-cysteine to 48.7 +/- 5.1% for CH(3)203Hg-albumin and approximately 60% for [14C]sucrose. Acivicin pretreatment significantly increased 203Hg excretion into bile after retrograde infusion of CH(3)203Hg-GSH, whereas 203Hg recovery after retrograde infusion of CH(3)203Hg-cysteine remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Biophysics, University of Rochester School of Medicine, New York.
W J
WJ
Dutczak
N
N
Ballatori
D000818:Animals; D001646:Bile / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D007555:Isoxazoles / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008767:Methylmercury Compounds / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000502:physiology*
D007555:Isoxazoles; D008767:Methylmercury Compounds; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine; C006303:acivicin