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

Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo. Am J Physiol Renal Physiol 287: F1067-F1075, 2004. First published July 27, 2004; doi:10.1152/ajprenal.00120.2004.--This study investigates the effect in rats of acute Cd[Cl.sub.2] (5 [micro]M) intoxication on renal function and characterizes the transport of [Ca.sup.2+], [Cd.sup.2+], and [Zn.sup.2+] 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 [Cd.sup.2+] injection resulted in renal losses of [Na.sup.+], [K.sup.+], [Ca.sup.2+], [Mg.sup.2+], P[O.sup.-2.sub.4], and water, but the glomerular filtration rate remained stable. [sup.45]Ca microinjections showed that [Ca.sup.2+] permeability in the DT was strongly inhibited by [Cd.sup.2+] (20 [micro]M), [Gd.sup.3+] (100 [micro]M), and [La.sup.3+] (1 mM), whereas nifedipine (20 [micro]M) had no effect, [sup.109]Cd and [sup.65][Zn.sup.2+] microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of [sup.109]Cd were taken up. [sup.109]Cd fluxes were inhibited by [Gd.sup.3+] (90 [micro]M), [Co.sup.2+] (100 [micro]M), and [Fe.sup.2+] (100 [micro]M) in all nephron segments. Bumetanide (50 [micro]M) only inhibited [sup.109]Cd fluxes in LH; [Zn.sup.2+] (50 and 500 [micro]M) inhibited transport of [sup.109]Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute [Cd.sup.2+] intoxication are suggestive of proximal tubulopathy; 2) [Cd.sup.2+] inhibits [Ca.sup.2+] reabsorption possibly through the epithelial [Ca.sup.2+] channel in the DT, and this blockade could account for the hypercalciuria associated with [Cd.sup.2+] intoxication; 3) the PT is the major site of [Cd.sup.2+] reabsorption; 4) the paracellular pathway and DMT1 could be involved in [Cd.sup.2+] reabsorption along the LH; 5) DMT1 may be one of the major transporters of [Cd.sup.2+] in the DT; and 6) [Zn.sup.2+] is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1. heavy metals; epithelial calcium channel; divalent metal transporter 1; kidney