Tubular secretion and reabsorption of mercury compounds in mouse kidney.
To determine whether Hg accumulated in renal cells is secreted into the lumen of proximal tubules with intracellular glutathione (GSH) and reabsorbed by tubular cells via a gamma-glutamyltranspeptidase (gamma-GTP)-dependent process as in the case of GSH itself, the effect of postadministration of acivicin (1 mmol/kg i.p.), a gamma-GTP inhibitor, on renal Hg accumulation was investigated in mice. Renal Hg content 4 hr after injection of CH3HgCl or HgCl2 (5 mumol/kg i.v.) was decreased to 35 or 44% of control, respectively, but urinary Hg excretion was increased by acivicin administration 2 hr after injection of the mercurials. When renal GSH was decreased to 19% of control by treatment with DL-buthionine-S,R-sulfoximine (4 mmol/kg s.c.) 2 hr before acivicin injection, the increase in urinary Hg excretion caused by acivicin was suppressed. Acivicin administration 24 hr after injection of the mercurials decreased renal methylmercury content determined 2 hr after acivicin injection and increased urinary Hg excretion. The postadministration of acivicin, however, did not affect the renal content of inorganic Hg which predominantly bound to metallothionein (MT) induced by HgCl2 itself. Pretreatment with Bi(NO3)3 as a renal MT inducer diminished the effect of acivicin administered 2 hr after HgCl2 injection on renal Hg content and urinary excretion. These results suggest that methylmercury and inorganic Hg bound to ligands other than MT in renal cytosol may be secreted into the lumen of proximal tubules with intracellular GSH and be reabsorbed via a gamma-GTP-dependent process.
Tanaka-Kagawa
T
T
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Naganuma
A
A
Imura
N
N
D000042:Absorption; D000818:Animals; D001729:Bismuth / Q000494:pharmacology; D005978:Glutathione / Q000652:urine; D007555:Isoxazoles / Q000494:pharmacology; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008628:Mercury / Q000493:pharmacokinetics*; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009566:Nitrates / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000502:physiology
D007555:Isoxazoles; D009566:Nitrates; C065545:bismuth nitrate; D008668:Metallothionein; D005723:gamma-Glutamyltransferase; D008628:Mercury; D005978:Glutathione; C006303:acivicin; D001729:Bismuth