Lead perturbs 1,25 dihydroxyvitamin D3 modulation of intracellular calcium metabolism in clonal rat osteoblastic (ROS 17/2.8) cells.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to modulate Ca2+ metabolism in several cell types. 1,25(OH)2D3 causes an increase in Ca2+ influx and probably exerts many of its effects via the Ca2+ messenger system. Lead (Pb2+) interacts with and perturbs normal Ca2+ signalling pathways; hence, the purpose of this work was to determine if Pb2+ perturbs 1,25(OH)2D3 modulation of Ca2+ metabolism in ROS 17/2.8 cells, which express receptors for and respond to 1,25(OH)2D3, and to determine the effect of 1,25(OH)2D3 on Pb2+ metabolism in these cells. In both cases three kinetic compartments described the intracellular metabolism of the isotope. These data show that 1 microM Pb2+ inhibits 1,25(OH)2D3 modulated increases in Ca2+ flux, whereas 5 microM Pb2+ increases membrane fluxes, all intracellular Ca2+ pools, and total cell Ca2+. In the Pb2+ metabolism studies it was found that 10 nM 1,25(OH)2D3 increases intracellular Pb2+. Pb2+ appears to disrupt the modulation of intracellular steady-state Ca2+ homeostasis by 1,25(OH)2D3 in a complex, biphasic manner and may therefore perturb functions that are modulated by 1,25(OH)2D3 via the Ca2+ messenger system.
Long
G J
GJ
Department of Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Rosen
J F
JF
D000818:Animals; D001859:Bone Neoplasms; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002999:Clone Cells; D004347:Drug Interactions; D006706:Homeostasis; D007700:Kinetics; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects
D002250:Carbon Radioisotopes; D009942:Organometallic Compounds; D002117:Calcitriol; C008261:lead acetate; D002118:Calcium