Complexing activity and excretion of 2,3-dimercapto-1-propane sulfonate in rat kidney.
The renal handling of the heavy metal complexing agent, 2,3-dimercapto-1-propane sulfonate (DMPS), was examined in the isolated perfused rat kidney (IPRK). Net tubular secretion of DMPS was saturable and blocked by p-aminohippuric acid (PAH) and probenecid (PRB), indicating involvement of carrier-mediated transport in the excretion of DMPS. DMPS was oxidized to a disulfide form (DMPSS) in perfusate and reduced to a sulfhydryl form (DMPSH) in kidney. In kidneys isolated from rats pretreated with HgCl2, DMPS produced a dose-dependent decrease in retention of inorganic mercury, an increase in urinary excretion of mercury, and an increase in the amount of mercury transferred from kidney into venous perfusate. At a maximally effective dose, 40% of the renal mercury content was excreted in urine during 30 min of perfusion. Urinary excretion of mercury induced by DMPS was completely blocked by concentrations of PRB that blocked tubular secretion of DMPS and decreased uptake of DMPS in kidney. Thus tubular secretion of DMPS and reduction of DMPSS to DMPSH are important in the renal handling of DMPS and may contribute to the activity of DMPS as a complexing agent for renal mercury.
Klotzbach
J M
JM
Department of Pharmacology and Environmental Health Sciences Center, School of Medicine and Dentistry, University of Rochester, New York 14642.
Diamond
G L
GL
D000818:Animals; D002250:Carbon Radioisotopes; D004112:Dimercaprol / Q000031:analogs & derivatives*; D004231:Diuresis / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010477:Perfusion; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D012079:Renal Circulation; D014494:Unithiol / Q000378:metabolism / Q000493:pharmacokinetics*; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D002250:Carbon Radioisotopes; D004112:Dimercaprol; D014494:Unithiol; D011339:Probenecid; D010130:p-Aminohippuric Acid