Parathyroid hormone-stimulated cadmium accumulation in Madin-Darby canine kidney cells

Abstract

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 Cd 2+ 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 109CdCl 2 accumulation in a concentration-dependent manner over the range of 10 −11–10 −9 m bPTH[1–34]. At 10 −9 m, PTH increased Cd 2+ accumulation maximally by 205%. The PTH antagonist, bPTH[3–34], failed to augment 109Cd 2+ accumulation. The dihydropyridine agonist, Bay k 8644, in the presence of PTH, increased 109Cd 2+ uptake by 200% over vehicletreated controls and by ≈ 100% over PTH or Bay k 8644 alone. The apparent K m for Bay k 8644 activation was 1.3 μ m. Bay k 8644-augmented 109Cd 2+ uptake was competitively inhibited by the calcium channel antagonist nifedipine. No voltage dependence of Bay k 8644-amplified 109Cd 2+ uptake could be detected. Based on these observations we conclude: (1) MDCK cells accumulate Cd 2+; (2) PTH increases Cd 2+ uptake into MDCK cells; and (3) Cd 2+ entry in kidney epithelial cells is mediated, at least in part, by dihydropyridine-sensitive calcium channels.