Effects of mercuric chloride on renal plasma membrane function after depletion or elevation of renal glutathione.
The role of renal nonprotein sulfhydryls (NPSH) in mercuric chloride-induced nephrotoxicity has been studied in various laboratories. Similarly, the importance of NPSH for mercuric ion accumulation by renal tissue also has been studied. In this study the potential role of NPSH was examined with respect to mercuric ion effects on membrane transport utilizing isolated membrane vesicles prepared from Sprague-Dawley rat kidneys. Sodium gradient-driven p-aminohippurate (PAH) transport in basolateral vesicles and glucose transport in brush border vesicles were studied. Depletion of NPSH, primarily glutathione (GSH), appeared to alter PAH but not glucose transport. HgCl2 (1 mg/kg) had no effect on either transport system in vesicles isolated from kidneys with normal GSH content, but it markedly disrupted both PAH and glucose transport in vesicles isolated from GSH-depleted rats. The most consistent effects were observed after GSH depletion with diethyl maleate plus buthionine sulfoximine. Elevation of renal GSH by administration of glutathione monoethyl ester blocked the effect of mercuric chloride (4 mg/kg) on glucose transport reported earlier. These data indicate that renal sulfhydryls not only modulate the effects of mercuric chloride, but they also may be important for normal physiological functioning of the PAH transport system.
Ansari
R A
RA
Department of Pharmacology, College of Medicine, University of Nebraska Medical Center, Omaha 68198-6810.
Thakran
R S
RS
Berndt
W O
WO
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D019328:Buthionine Sulfoximine; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008627:Mercuric Chloride / Q000009:adverse effects / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism
D008298:Maleates; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008627:Mercuric Chloride; C042431:S-ethyl glutathione; C014476:diethyl maleate; D005978:Glutathione; D005947:Glucose; D010130:p-Aminohippuric Acid