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

Miscellaneous · Mon Jan 01 00:00:00 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
• Resource Relation: Other Information: Thesis (Ph.D.)
• Country of Publication: United States
• Language: English

Related Subjects

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