Evidence of active transport of cadmium complexing dithiocarbamates into renal and hepatic cells in vivo.
A study was made of the effects of certain inhibitors of transport systems on the actions of four cadmium (Cd) complexing N,N-disubstituted dithiocarbamates (DTCs) in mobilizing murine renal and hepatic Cd in vivo. Probenecid, the prototypical antagonist of organic anion transport in the kidney, when given 1 hr prior to each DTC, sharply suppressed the DTC-induced reduction of renal Cd but was virtually without effect on mobilization of Cd from liver. Sulfinpyrazone, which blocks tubular reabsorption of uric acid and also inhibits transport of a variety of organic acids, inhibited markedly the mobilization of both renal and hepatic Cd by DTCs. Phlorizin, an inhibitor of tubular sugar reabsorption, did not affect the Cd mobilizing actions of DTCs in any consistent fashion. We propose that the high degree of selectivity of DTCs in mobilizing renal and hepatic Cd is dependent, at least in part, upon active transport of DTCs into these tissues via the organic anion transport systems. This report presents the first evidence that compounds of the (R)2NCSS- class may gain access to intracellular space by an active, carrier-mediated process.
Gale
G R
GR
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC 29401-5799.
Smith
A B
AB
Jones
M M
MM
Singh
P K
PK
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002104:Cadmium / Q000378:metabolism*; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D011339:Probenecid / Q000494:pharmacology; D013859:Thiocarbamates / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D013859:Thiocarbamates; D002104:Cadmium; D011339:Probenecid