Basolateral uptake of mercuric conjugates of N-acetylcysteine and cysteine in the kidney involves the organic anion transport system.
Renal uptake and disposition of administered inorganic mercury were studied in rats that had undergone an acute bilateral ureteral ligation shortly before being injected intravenously with a nontoxic 0.5 micromol/kg dose of inorganic mercury with or without 2 micromol/kg N-acetylcysteine or cysteine. Bilateral ureteral ligation was performed in an attempt to reduce glomerular filtration to negligible levels, which in turn permitted the study of the basolateral uptake of inorganic mercury. The disposition of mercury was studied in the kidneys, liver, and blood 1 h after treatment. In rats given only mercuric chloride, the renal burden of mercury was approximately 20% of the administered dose of mercury. This confirms previous observations implicating a basolateral mechanism in the renal uptake of inorganic mercury. Coadministration of inorganic mercury with either N-acetylcysteine or cysteine caused a significant increase in the renal uptake of mercury 1 h after treatment, particularly in the rats treated with inorganic mercury plus N-acetylcysteine. The enhanced uptake of mercury in the kidneys was due to increased uptake of mercury in the renal cortex and outer stripe of the outer medulla. Interestingly, the rate of uptake of mercury was so great in the rats treated with inorganic mercury plus N-acetylcysteine that the renal burden of mercury was virtually equivalent to that generally detected in normal animals administered the same dose of inorganic mercury as mercuric chloride. Pretreatment with para-aminohippuric acid (PAH) (which is a potent inhibitor of the organic anion transport system) caused significant reductions in the renal uptake and burden of inorganic mercury in all the rats administered inorganic mercury, regardless of whether the inorganic mercury was coadministered with N-acetylcysteine or cysteine. Overall, the findings from the present study provide additional evidence that there is basolateral uptake of inorganic mercury in the kidneys, and that the primary or sole mechanism is dependent on the activity of the organic anion transporter. The present findings also show that cysteine and N-acetylcysteine enhance the basolateral uptake of mercuric ions in the kidney when they are coadministered with inorganic mercury, presumably in the form of mercuric conjugates. Moreover, it appears that mercuric conjugates of N-acetylcysteine are taken up more avidly at the basolateral membrane than mercuric conjugates of cysteine. Furthermore, the basolateral uptake of mercuric conjugates of N-acetylcysteine or cysteine in the kidney is due primarily to a mechanism involving the organic anion transport system.
Zalups
R K
RK
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia, USA.
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins; D001692:Biological Transport; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D003545:Cysteine / Q000494:pharmacology; D004338:Drug Combinations; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014513:Ureter / Q000601:surgery; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D004338:Drug Combinations; D008627:Mercuric Chloride; D003545:Cysteine; D000111:Acetylcysteine; D010130:p-Aminohippuric Acid