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

The specific uptake of 0.3 muM Cd-109 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 Cd-109(2+), relative to total Cd-109, was increased. The initial uptake rate was 12-fold higher under conditions, optimizing Cd-109(2+) accumulation over that of (CdCln2-n)-Cd-109 (NO3-/pH(out) 5.5); a saturable system of transport has been characterized (K-m = 1.1 +/- 0.1 muM, V-max = 87 +/- 3 pmol/3 min/mg protein). An excess of Fe2+ failed to affect Cd-109 uptake when the pH(out) was 7.4, whereas a strong inhibition was observed under NO3-/pH(out) 5.5 conditions. In contrast, the maximal inhibitory effect of Zn2+ was observed under Cl-/pH(out) 7.4 conditions. This results strongly suggest that Fe2+ may compete with Cd2+ for Nramp2, whereas Zn and CdCln2-n compete for another system of transport that has yet to be identified. (C) 2001 Academic Press.