Acute cadmium uptake by rabbit kidneys: mechanism and effects.
Trapping of an arterial bolus in the kidney by 40 sec aortic occlusion permitted demonstration of diffusion-limited and Zn-sensitive renal uptake of nonfiltered but diffusible Cd from plasma; mercaptoethanol (ME) or 2,3-dimercaptopropanol (BAL) had been added to the bolus to prevent sequestration of the metals by plasma protein. Cadmium taken up by the kidney under these conditions, whether from blood or glomerular filtrate, unlike Zn, did not return to blood over a period of 2-3 min. Nor was Cd thus accumulated removed by EDTA; it had presumably been transferred into cells. The diffusion dependence of this internalization shows it to be a relatively slow process, as it is in jejunum. In contrast, uptake of Cd tightly bound in a lipid-soluble complex with diethyldithiocarbamate (DDTC) is rapid and flow dependent. Slow uptake in the presence of ME and its inhibition by Zn are therefore not likely to involve movement of undissociated ME complex across the cell membranes. Instead, it is suggested that (1) Cd-binding sites on the membrane possess a relatively high affinity for Cd and can compete for it with ME, and (2) it is the resulting Cd-membrane interaction which, as in jejunum, is depressed by Zn. During transient occlusion kidneys could be loaded with up to 25 micrograms Cd/g cortex without evidence of immediate malfunction. Inhibition of amino acid transport, as previously described, is seen only after an initiation period of 1-2 days following CdME injection, although cortical Cd levels at that time have decreased. The finding of a slowly developing inhibition of amino acid carrier systems suggests an indirect action of Cd; by implication, unique threshold concentrations should not be defined for Cd in renal cortex following subchronic exposures without reference to the duration of exposure.
Foulkes
E C
EC
Department of Environmental Health, University of Cincinnati College of Medicine, Ohio 45267-0056.
Blanck
S
S
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D015032:Zinc / Q000494:pharmacology
D000596:Amino Acids; D002104:Cadmium; D015032:Zinc