The effects of parathyroid hormone and estradiol on cadmium accumulation by Madin-Darby canine kidney cells

Thesis/Dissertation · Mon Jan 01 04:00:00 EST 1990

OSTI ID:7013344

Flanagan, J L

Chronic exposure to the toxic metal cadmium causes osteomalacia, osteoporosis, increased serum parathyroid hormone, renal stone formation, hypercalciuria and renal tubular dysfunction, reflecting one or more disturbances of calcium homeostasis. Since renal cadmium (Cd[sup 2+]) transport proceeds in both proximal and distal tubules and parathyroid hormone (PTH) regulates calcium reabsorption at distal nephron sites, it was postulated that PTH may also stimulate Cd[sup 2+] transport in distal tubules. Madin-Darby canine kidney (MDCK) cells, which express a distal phenotype including PTH-sensitive adenylate cyclase and calcium transport, were used as the cell model for the present study. Cadmium uptake was measured using [[sup 109]Cd[sup 2+]] and a rapid filtration technique. Bovine parathyroid hormone (bPTH[1-34]) stimulated concentration-dependent increases in [[sup 109]Cd[sup 2+]] accumulation. The PTH analogue bPTH[3-34], a PTH antagonist, had no effect on [[sup 109]Cd[sup 2+]] accumulation demonstrating the specificity of PTH stimulation. Bay k 8644, a dihydropyridine-type calcium channel agonist, amplified PTH-stimulated [[sup 109]Cd[sup 2+]] accumulation. This effect was blocked by nifedipine, a dihydropyridine-type calcium channel antagonist. These results indicate first that Cd[sup 2+] uptake is mediated by dihydropyridine-sensitive calcium channels and second, that in the absence of PTH, few channels are active. Altering membrane potential with extracellular [K[sup +]] manipulations had no effect on [[sup 109]Cd[sup 2+]] uptake. Ethynylestradiol (EE) produced dose-dependent increases in PTH-stimulated [[sup 109]Cd[sup 2+]] accumulation with addition of 10[sup [minus]12] to 10[sup [minus]8] M EE. PTH receptor cross-linking and binding assays indicated that in the presence of bPTH[1-34], EE increased PTH-receptor protein density in the presence of bPTH[1-34].

• Research Organization: Dartmouth Coll., Hanover, NH (United States)
• OSTI ID: 7013344
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL ACCUMULATION
BODY
CADMIUM
CADMIUM 109
CADMIUM ISOTOPES
CALCIUM
CELL CULTURES
CLEARANCE
DATA
DOGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ESTRADIOL
ESTRANES
ESTROGENS
EVEN-ODD NUCLEI
EXCRETION
EXPERIMENTAL DATA
HORMONES
HYDROXY COMPOUNDS
INFORMATION
INTERMEDIATE MASS NUCLEI
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
METABOLISM
METALS
NUCLEI
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
PARATHORMONE
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RENAL CLEARANCE
STEROID HORMONES
STEROIDS
TOXICITY
TUBULES
VERTEBRATES
YEARS LIVING RADIOISOTOPES