INHIBITION OF NA-GLUCOSE COTRANSPORT IN KIDNEY CORTICAL-CELLS BY CADMIUM AND COPPER - PROTECTION BY ZINC()

Properties of the inhibition of Na+-glucose cotransport by Cd2+ in mou se kidney cortical cells have been determined. In no case was any inhi bition observed before 3 hr. The extent of inhibition was dependent up on both the concentration of Cd2+ and the length of exposure. Kinetic studies showed that metallothionein mRNA induction by Cd2+ was initiat ed within 1 hr after incubation with Cd2+ began and peaked by 3-6 hr. Metallothionein protein increased more slowly, beginning at 3 hr and c ontinuing for at least 9 hr. The protein had both Cd2+ and Zn2+ bound to it throughout this period. Nevertheless, a pool of nonmetallothione in Cd2+ appeared after 3 hr, coinciding with the onset of inhibition o f Na+-glucose cotransport, and increased over the next 9 hr. Pretreatm ent of cells with Zn2+ protected them from the effects of Cd2+ on Na+- glucose cotransport. It delayed the onset of inhibition of transport a s well as the extent of inhibition. Detailed analysis of the distribut ion of Cd2+ and Zn2+ in the soluble fraction of these cells showed tha t the concentration of non-metallothionein bound Cd2+ was not suppress ed by the presence of Zn-metallothionein after the onset of exposure t o Cd2+ Incubation of cells with larger concentration of Zn2+ and Cu2also inhibited Na+-glucose cotransport. (C) 1994 Academic Press, Inc.