Cadmium uptake through the anion exchanger in human red blood cells.
1. The initial rate of Cd2+ uptake in human red cells was measured by atomic absorption spectrophotometry. 2. About 96% of Cd2+ uptake was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) with IC50 (concentration giving 50% of maximal inhibition) of 0.3 microM and by furosemide with IC50 of 500 microM and was resistant to ouabain and amiloride. This indicates the implication of the [Cl(-)-HCO3-] anion exchanger in Cd2+ uptake. 3. DIDS-sensitive Cd2+ uptake required the presence of external HCO3-. HCO3- ions had a biphasic effect on Cd2+ uptake. Low bicarbonate concentrations were stimulatory, suggesting formation of translocating bicarbonate-cadmium complexes. Higher bicarbonate concentrations were inhibitory, suggesting further bicarbonate complexation with formation of non-translocating species. Depending on the presence or absence of external Cl-, a maximal Cd2+ uptake of 1.7 or 0.37 mmol (l cells)-1 h-1 was observed at bicarbonate concentrations of 15.6 or 11 mM respectively. 4. In the presence of bicarbonate, external Cl- ions strongly stimulated Cd2+ uptake, with linear increase between 70 and 125 mM. This suggests that one translocating species may have chloride as ligand. 5. DIDS-sensitive Cd2+ uptake was modestly inhibited by physiological concentrations of external phosphate and was resistant to external K+, Mg2+ and Ca2+. 6. In conclusion, the anion exchanger is the major transport mechanism for red cell cadmium uptake. Translocating species appear to be monovalent anion complexes of cadmium with HCO3- such as [Cd(OH)(HCO3)2]- and [Cd(OH)(HCO3)Cl]-.
Lou
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M
Departamento de Fisiología, Facultad de Medicina, Zaragoza, Spain.
Garay
R
R
Alda
J O
JO
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000838:Anions / Q000378:metabolism; D001639:Bicarbonates / Q000494:pharmacology; D002104:Cadmium / Q000378:metabolism* / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010710:Phosphates / Q000494:pharmacology; D013054:Spectrophotometry, Atomic
D000838:Anions; D001639:Bicarbonates; D002712:Chlorides; D010710:Phosphates; D002104:Cadmium; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid