Mechanism of mobilization of cadmium by dithiocarbamates in rat primary hepatocyte cultures.
The mechanism of mobilization of cadmium (Cd) by N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) in rat primary hepatocyte cultures was studied. Probenecid pretreatment increased Cd efflux from the hepatocytes by BGD, but did not affect Cd efflux by HBGD. p-Aminohippurate treatment had no effect on Cd efflux by the chelating agents. These results suggest that an enhancing effect of probenecid on the BGD-induced Cd mobilization is due to its inhibitory effect on the glucuronidation of BGD and not its specific action on BGD transport. Verapamil and nicardipine had no effect on the chelating agent-induced Cd mobilization. Phlorizin did not affect Cd efflux by BGD or HBGD. Phloretin and cytochalasin B inhibited Cd efflux by the chelating agents. These results seem to be evidence that BGD and HBGD may be transported by a facilitated diffusion system in the hepatocytes.
Funakoshi
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Ueda
K
K
Kado
K
K
Kojima
S
S
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010695:Phlorhizin / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013859:Thiocarbamates / Q000493:pharmacokinetics / Q000494:pharmacology*
D002614:Chelating Agents; D013859:Thiocarbamates; D002104:Cadmium; D013012:Sorbitol; D010695:Phlorhizin; C048763:N-benzylglucamine dithiocarbamate; D011339:Probenecid