Parathyroid hormone-stimulated cadmium accumulation in Madin-Darby canine kidney cells.
Although most renal cadmium transport occurs in proximal tubules indirect evidence suggests that distal tubules may also transport this heavy metal. Since the distal nephron is the site at which parathyroid hormone (PTH) regulates calcium absorption, we evaluated the effects of PTH on Cd2+ accumulation in Madin-Darby canine kidney (MDCK) cells. MDCK cells express a distal-like phenotype including PTH-sensitive adenylyl cyclase and stimulation of calcium transport. MDCK cells were grown to confluence in phenol red-free Dulbecco's modified Eagle's medium. PTH increased 109CdCl2 accumulation in a concentration-dependent manner over the range of 10(-11)-10(-9) M bPTH[1-34]. At 10(-9) M, PTH increased Cd2+ accumulation maximally by 205%. The PTH antagonist, bPTH[3-34], failed to augment 109Cd2+ accumulation. The dihydropyridine agonist, Bay k 8644, in the presence of PTH, increased 109Cd2+ uptake by 200% over vehicle-treated controls and by approximately 100% over PTH or Bay k 8644 alone. The apparent Km for Bay k 8644 activation was 1.3 microM. Bay k 8644-augmented 109Cd2+ uptake was competitively inhibited by the calcium channel antagonist nifedipine. No voltage dependence of Bay k 8644-amplified 109Cd2+ uptake could be detected. Based on these observations we conclude: (1) MDCK cells accumulate Cd2+; (2) PTH increases Cd2+ uptake into MDCK cells; and (3) Cd2+ entry in kidney epithelial cells is mediated, at least in part, by dihydropyridine-sensitive calcium channels.
Flanagan
J L
JL
Dartmouth Medical School, Department of Pharmacology & Toxicology, Hanover, New Hampshire 03756.
Friedman
P A
PA
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D004285:Dogs; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013268:Stimulation, Chemical
D015220:Calcium Channels; D004095:Dihydropyridines; D010281:Parathyroid Hormone; D002104:Cadmium; C038806:1,4-dihydropyridine