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 CdCl(2) (5 microM) intoxication on renal function and characterizes the transport of Ca(2+), Cd(2+), and Zn(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(2+) injection resulted in renal losses of Na(+), K(+), Ca(2+), Mg(2+), PO(4)(-2), and water, but the glomerular filtration rate remained stable. (45)Ca microinjections showed that Ca(2+) permeability in the DT was strongly inhibited by Cd(2+) (20 microM), Gd(3+) (100 microM), and La(3+) (1 mM), whereas nifedipine (20 microM) had no effect. (109)Cd and (65)Zn(2+) 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(3+) (90 microM), Co(2+) (100 microM), and Fe(2+) (100 microM) in all nephron segments. Bumetanide (50 microM) only inhibited (109)Cd fluxes in LH; Zn(2+) (50 and 500 microM) inhibited transport of (109)Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd(2+) intoxication are suggestive of proximal tubulopathy; 2) Cd(2+) inhibits Ca(2+) reabsorption possibly through the epithelial Ca(2+) channel in the DT, and this blockade could account for the hypercalciuria associated with Cd(2+) intoxication; 3) the PT is the major site of Cd(2+) reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd(2+) reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd(2+) in the DT; and 6) Zn(2+) is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1.
UMR-CNRS 6548, Bâtiment Sciences Naturelles, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
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Barbier
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Jacquillet
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Tauc
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Poujeol
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Cougnon
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002034:Bumetanide / Q000494:pharmacology; D002104:Cadmium / Q000378:metabolism*; D002105:Cadmium Poisoning / Q000378:metabolism; D002106:Cadmium Radioisotopes; D002118:Calcium / Q000378:metabolism* / Q000652:urine; D002132:Calcium Radioisotopes; D027682:Cation Transport Proteins / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D033862:Iron-Binding Proteins / Q000378:metabolism; D007677:Kidney Function Tests; D008845:Microinjections; D009399:Nephrons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000378:metabolism*; D015037:Zinc Radioisotopes; D000099236:Solute Carrier Family 11, Member 2
D002034:Bumetanide; D002104:Cadmium; D002106:Cadmium Radioisotopes; D002118:Calcium; D002132:Calcium Radioisotopes; D027682:Cation Transport Proteins; D002412:Cations; D004232:Diuretics; D033862:Iron-Binding Proteins; D015032:Zinc; D015037:Zinc Radioisotopes; D000099236:Solute Carrier Family 11, Member 2