Differences in cadmium and mercury uptakes by hepatocytes: role of calcium channels.
Calcium uptake in cells occurs through specific membrane channels. Since cadmium and mercury inhibit calcium uptake, this study examined whether the calcium channels may also be involved in the uptake of these metals. Primary cultures of rat hepatocytes were incubated with 3 microM CdCl2 or HgCl2 in the absence or presence of four different organic calcium channel blockers or a calcium agonist. The calcium channel blockers had no significant effect on mercury accumulation. In comparison, the uptake of cadmium was inhibited by diltiazem and verapmil (50-250 microM) as well as by nifedipine and nitrendipine (25-100 microM), with a maximum inhibition of 31% after 30 min incubation with 250 microM verapamil. The calcium agonist vasopressin (20 nM) increased cadmium accumulation by 15%. This effect was blocked by 250 microM verapamil. Kinetic analysis showed that verapamil decreased the Vmax of cadmium uptake, without altering the Km, indicating a noncompetitive inhibition. The calcium channel blockers were ineffective at 4 degrees C. These data suggest that about a third of the cadmium enters hepatocytes through the calcium channels. The mechanism of mercury uptake, on the other hand, is very different as it does not appear to involve the calcium channels.
Blazka
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ME
Department of Pharmacology and Toxicology, University of Rhode Island, Kingston 02881.
Shaikh
Z A
ZA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000378:metabolism* / Q000494:pharmacology; D019256:Cadmium Chloride; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008627:Mercuric Chloride / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002104:Cadmium; D004533:Egtazic Acid; D008627:Mercuric Chloride; D019256:Cadmium Chloride; D002118:Calcium