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

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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 and 65Zn2+ microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of 109Cd 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 inhibited 109Cd fluxes in LH; Zn2+ (50 and 500 μM) inhibited transport of 109Cd 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.
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