Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo

Abstract

This study investigates the effect in rats of acute CdCl2(5 μM) intoxication on renal function and characterizes the transport of Ca2+, Cd2+, and Zn2+in the proximal tubule (PT), loop of Henle (LH), and terminal segments of the nephron (DT) using whole kidney clearance and nephron microinjection techniques. Acute Cd2+injection resulted in renal losses of Na+, K+, Ca2+, Mg2+, PO4−2, and water, but the glomerular filtration rate remained stable.45Ca microinjections showed that Ca2+permeability in the DT was strongly inhibited by Cd2+(20 μM), Gd3+(100 μM), and La3+(1 mM), whereas nifedipine (20 μM) had no effect.109Cd and65Zn2+microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of109Cd were taken up.109Cd fluxes were inhibited by Gd3+(90 μM), Co2+(100 μM), and Fe2+(100 μM) in all nephron segments. Bumetanide (50 μM) only inhibited109Cd fluxes in LH; Zn2+(50 and 500 μM) inhibited transport of109Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd2+intoxication are suggestive of proximal tubulopathy; 2) Cd2+inhibits Ca2+reabsorption possibly through the epithelial Ca2+channel in the DT, and this blockade could account for the hypercalciuria associated with Cd2+intoxication; 3) the PT is the major site of Cd2+reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd2+reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd2+in the DT; and 6) Zn2+is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1.