EFFECTS OF ZINC AND COPPER ON CADMIUM UPTAKE BY BRUSH-BORDER MEMBRANE-VESICLES

The effects of essential metals, zinc (Zn) and copper (Cu), on cadmium (Cd) uptake were investigated in brush border membrane vesicles (BBMV ) isolated from the rat renal cortex and LLC-PK1 cells. BBMV were incu bated with Cd in the presence or absence of Zn or Cu, and then washed with a chelating agent, EGTA, to remove Cd bound to the outer surface of BBMV. Go-incubation with Zn or Cu decreased Cd accumulation in thes e BBMV in a concentration-dependent manner. Kinetic analysis of the in itial accumulation of Gd suggested that Cd is taken up into rat BBMV v ia an unsaturable component and a saturable component (K-m=13.8 mu M, V-max=1.44 nmol/mg protein/min), and co-incubation with Zn significant ly increased the K-m of the saturable component without affecting the V-max, whereas Cu significantly increased the K-m-value and decreased the V-max-value. Increasing the osmolarity of the incubation medium sl ightly decreased Cd accumulation in the absence of Zn or Cu, whereas i t did not decrease Cd accumulation in the presence of these metals. Th ese results suggest the possibility that, in addition to passive diffu sion, Cd is also taken up from the renal brush border membrane via car rier-mediated mechanisms that are inhibited by Zn competitively and by Cu non-competitively. Furthermore, these results suggest that: (1) Cd binds externally and internally to BBMV, (2) little Cd is transported into the intravesicular space, and (3) both Zn and Cu decrease the bi nding and transport of Cd. (C) 1997 Elsevier Science Ireland Ltd.