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

O. Barbier, G. Jacquillet, M. Tauc, P. Poujeol, M. Cougnon
2004 AJP - Renal Physiology  
Barbier, O., G. Jacquillet, M. Tauc, P. Poujeol, and M. Cougnon. Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo. This study investigates the effect in rats of acute CdCl2 (5 M) intoxication on renal function and characterizes the transport of Ca 2ϩ , Cd 2ϩ , and Zn 2ϩ 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 2ϩ
more » ... Acute Cd 2ϩ injection resulted in renal losses of Na ϩ , K ϩ , Ca 2ϩ , Mg 2ϩ , PO 4 Ϫ2 , and water, but the glomerular filtration rate remained stable. 45 Ca microinjections showed that Ca 2ϩ permeability in the DT was strongly inhibited by Cd 2ϩ (20 M), Gd 3ϩ (100 M), and La 3ϩ (1 mM), whereas nifedipine (20 M) had no effect. 109 Cd and 65 Zn 2ϩ microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of 109 Cd were taken up. 109 Cd fluxes were inhibited by Gd 3ϩ (90 M), Co 2ϩ (100 M), and Fe 2ϩ (100 M) in all nephron segments. Bumetanide (50 M) only inhibited 109 Cd fluxes in LH; Zn 2ϩ (50 and 500 M) inhibited transport of 109 Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd 2ϩ intoxication are suggestive of proximal tubulopathy; 2) Cd 2ϩ inhibits Ca 2ϩ reabsorption possibly through the epithelial Ca 2ϩ channel in the DT, and this blockade could account for the hypercalciuria associated with Cd 2ϩ intoxication; 3) the PT is the major site of Cd 2ϩ reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd 2ϩ reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd 2ϩ in the DT; and 6) Zn 2ϩ 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 CADMIUM (CD 2ϩ ) IS ONE OF THE most commonly found toxic metals present in our environment. The major sources of exposure to Cd 2ϩ are contaminated food and water, tobacco, and industrial fumes and dusts (16). Cd 2ϩ accumulates in the body, and chronic exposure causes severe nephrotoxicity in humans (16) and animals (2, 4). The renal dysfunction may be due to proximal tubular damage affecting the passive paracellular pathway (14, 27) and decreasing active transcellular ion transport (30). With the use of in vitro models, deleterious effects of Cd 2ϩ have been described on several solute transporters, such as stretch-activated ion channels (24), the epithelial Ca 2ϩ channel (ECaC) transporter (32), the NaPi-II transporter (19), the Na/glucose transporter (1), and the NaSi-1 transporter (25). These acute effects of Cd 2ϩ suggest the Address for reprint requests and other correspondence: P. Poujeol,
doi:10.1152/ajprenal.00120.2004 pmid:15280159 fatcat:4wjoh337uffehkcbwhyuuqalay