Routes for renal transport of methylmercury in mice.
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.
Tanaka
T
T
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Naganuma
A
A
Imura
N
N
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
D000963:Antimetabolites; D007555:Isoxazoles; D008767:Methylmercury Compounds; C030957:methylmercury II; D005978:Glutathione; C006303:acivicin; D011339:Probenecid