title: Routes for renal transport of methylmercury in mice.
abstract: To clarify the routes for renal methylmercury uptake, the effects of ureter ligation and pretreatment of probenecid, an organic anion transport inhibitor, or acivicin, a gamma-glutamyltranspeptidase (gamma-GTP) inhibitor, on renal methylmercury content were investigated in mice. For 120 min after CH3HgCl (5 mumol/kg, i.v.) injection, renal methylmercury content in bilateral ureter-ligated mice was approximately 50% lower than that of sham-operate mice. The glomerular filtration rate was reduced to about 15% of the control by ureter ligation. These results suggest an important role of glomerular filtration in the renal methylmercury uptake. Pretreatment with probenecid (0.5 or 1.0 mmol/kg, i.p.) reduced the renal methylmercury accumulation 30 min after CH3HgCl injection in a dose-dependent manner in both ureter-ligated and sham-operated mice. Urinary methylmercury excretion was not affected by probenecid pretreatment. Renal methylmercury content of ureter-ligated mice was not changed by pretreatment with acivicin (0.5 or 1.0 mmol/kg. i.p.), which was previously reported to decrease the renal methylmercury content in mice. Coadministration of GSH (10 mumol/kg, i.v.) with CH3HgCl increased the renal methylmercury uptake determined 5 min after injection in ureter-ligated mice. These results suggest that at least two transport systems play major roles in renal methylmercury uptake: one is a route from the glomeruli through the brush border membrane which is dependent on the action of gamma-GTP, and the other route is the one using an organic anion transport system through the basolateral membrane.
authors.affiliation: Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Naganuma
authors.forename: N
authors.initials: N
authors.lastname: Imura
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005978:Glutathione / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008767:Methylmercury Compounds / Q000493:pharmacokinetics*; D051379:Mice; D008813:Mice, Inbred ICR; D008871:Microvilli / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000963:Antimetabolites; D007555:Isoxazoles; D008767:Methylmercury Compounds; C030957:methylmercury II; D005978:Glutathione; C006303:acivicin; D011339:Probenecid