Evidence for cadmium uptake through Nramp2: metal speciation studies with Caco-2 cells.

The specific uptake of 0.3 microM (109)Cd by the TC7 clone of the human enterocytic-like Caco-2 cells increased 4-fold as the pH(out) was lowered from 7.5 to 5.5; the stimulatory effect of acidic media being more pronounced when the level of the free ion (109)Cd(2+), relative to total (109)Cd, was increased. The initial uptake rate was 12-fold higher under conditions, optimizing (109)Cd(2+) accumulation over that of (109)CdCl(2-n)(n) (NO(-)(3)/pH(out) 5.5); a saturable system of transport has been characterized (K(m) = 1.1 +/- 0.1 microM, V(max) = 87 +/- 3 pmol/3 min/mg protein). An excess of Fe(2+) failed to affect (109)Cd uptake when the pH(out) was 7.4, whereas a strong inhibition was observed under NO(-)(3)/pH(out) 5.5 conditions. In contrast, the maximal inhibitory effect of Zn(2+) was observed under Cl(-)/pH(out) 7.4 conditions. This results strongly suggest that Fe(2+) may compete with Cd(2+) for Nramp2, whereas Zn and CdCl(2-n)(n) compete for another system of transport that has yet to be identified.