Gale G R, Smith A B, Jones M M, Singh P K
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC 29401-5799.
Pharmacol Toxicol. 1992 Dec;71(6):452-6. doi: 10.1111/j.1600-0773.1992.tb00577.x.
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.
一项关于某些转运系统抑制剂对四种镉（Cd）络合的N，N-二取代二硫代氨基甲酸盐（DTCs）在体内动员小鼠肾脏和肝脏中镉的作用的研究。丙磺舒是肾脏中有机阴离子转运的典型拮抗剂，在每次给予DTC前1小时给药，可显著抑制DTC诱导的肾脏镉减少，但对肝脏镉的动员几乎没有影响。磺吡酮可阻止尿酸的肾小管重吸收，还抑制多种有机酸的转运，它显著抑制了DTCs对肾脏和肝脏镉的动员。根皮苷是一种肾小管糖重吸收抑制剂，它对DTCs的镉动员作用没有任何一致的影响。我们提出，DTCs在动员肾脏和肝脏镉方面的高度选择性至少部分取决于DTCs通过有机阴离子转运系统主动转运进入这些组织。本报告首次证明（R）2NCSS-类化合物可能通过主动的、载体介导的过程进入细胞内空间。
