Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 1997 Mar 28;272(13):8346-52.

Cellular uptake of lead is activated by depletion of intracellular calcium stores.

Author information

1
Department of Pharmacology and Physiology and the Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.

Abstract

The mechanisms of cellular lead uptake were characterized using a fluorescence method in cells loaded with indo-1. Pb2+ bound to intracellular indo-1 with much higher affinity than Ca2+ and quenched fluorescence at all wavelengths. Pb2+ uptake into pituitary GH3 cells, glial C6 cells, and a subclone of HEK293 cells was assessed by fluorescence quench at a Ca2+-insensitive emission wavelength. Pb2+ uptake was concentration- and time-dependent. Pb2+ uptake in all three cell types occurred at a much faster rate when intracellular Ca2+ stores were depleted by two different methods: addition of drugs that inhibit the endoplasmic reticulum Ca2+ pump (thapsigargin, cyclopiazonic acid, and tert-butylhydroquinone), and prolonged incubation of cells in Ca2+-free media. Application of receptor agonists, which deplete intracellular Ca2+ stores via inositol trisphosphate-sensitive channels, did not activate Pb2+ uptake. Agonists were just as effective as thapsigargin in stimulating uptake of Ca2+ but less so in stimulating uptake of Mn2+. Basal and stimulated Pb2+ uptake were partially reduced by 1 mM extracellular Ca2+ and strongly inhibited by 10 mM Ca2+. Pb2+ entry in GH3 cells was inhibited by two drugs that block capacitative Ca2+ entry, La3+ and SK&F 96365. Depolarization of electrically excitable GH3 cells increased the initial rate of Pb2+ uptake 1.6-fold, whereas thapsigargin increased uptake 12-fold. In conclusion, Pb2+ crosses the plasma membrane of GH3, C6, and HEK293 cells via channels that are activated by profound depletion of intracellular Ca2+ stores.

PMID:
9079658
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center