Cadmium uptake by kidney distal convoluted tubule cells.
Cadmium is transported by and accumulated in the kidney, which is a primary site of its toxicity. Most cadmium is reabsorbed and accumulated by proximal tubules. However, evidence for distal tubule toxicity suggests that transport may also proceed at that nephron site. Therefore, we measured cadmium uptake by an immortalized distal convoluted tubule (DCT) cell line. Absolute rates of cadmium uptake averaged 0.43 nmol min-1 mg protein-1, about 20% of the rate of calcium uptake, at an extracellular calcium ([Ca]o) concentration of 1 mM. As [Ca]o was reduced below 1 mM, cadmium uptake increased in a stepwise fashion. When [Ca]o was raised above 1 mM, cadmium uptake diminished proportionately. These results support the view that calcium and cadmium compete for the same transport mechanism in DCT cells. We also examined the interaction of cadmium on cadmium uptake, as well as the effects of selected di- and trivalent cations on cadmium transport. The resulting inhibitory sequence was Fe > La = Mn > Co > Cu = Mg > Zn > Cd > Ni = Sr > Ca. Bay k 8644 enhanced and nifedipine abolished cadmium uptake that was stimulated by parathyroid hormone (PTH). However, neither Bay k 8644 nor nifedipine altered basal cadmium uptake. We conclude that cadmium is taken up by distal convoluted tubule cells. Under resting conditions cadmium entry is mediated by a mechanism that is insensitive to calcium channel agonists or antagonists. Cadmium entry stimulated by PTH is mediated by dihydropyridine-sensitive calcium channels.
Friedman
P A
PA
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755.
Gesek
F A
FA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002413:Cations, Divalent / Q000494:pharmacology; D002461:Cell Line, Transformed; D004095:Dihydropyridines / Q000494:pharmacology; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology
D015220:Calcium Channels; D002413:Cations, Divalent; D004095:Dihydropyridines; D010281:Parathyroid Hormone; D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium