Lead increases inositol 1,4,5-trisphosphate levels but does not interfere with calcium transients in primary rat astrocytes.
Alteration of receptor-mediated signal transduction pathways by inorganic lead (Pb) has been postulated to contribute to the neurotoxicity of this environmental toxicant, some of these effects involving astrocytes. As Pb is known to mimic Ca2+ in various biological systems or alter Ca(2+)-mediated cellular processes, we analyzed the effect of Pb exposure on alpha 1 receptor activated astrocytic phosphoinositide metabolism and Ca2+ responses in primary astrocyte cultures prepared from cerebral cortex of 1-day-old rats. Exposure to norepinephrine (NE; 10-100 microM) resulted in a significant increase in astrocytic inositol 1,4,5-trisphosphate levels, concomitant with an increase in intracellular Ca2+ levels. Fifteen minute exposure to Pb (10 microM lead acetate) significantly increased inositol 1,4,5-trisphosphate generation compared with controls, both in the presence and absence of NE. However, the inositol 1,4,5-trisphosphate-mediated Ca2+ transients following NE stimulation was unaltered in the presence of Pb (1-100 microM). NE-evoked intracellular Ca2+ responses, both in the presence and absence of extracellular Ca2+ did not differ between control and Pb-treated astrocytes. Additional studies failed to demonstrate the occurrence of Pb influx into astrocytes within the first 12 min of exposure such that Ca2+ responses would be directly affected. It therefore appears unlikely that astrotoxic effects of Pb are mediated via direct changes in intracellular Ca2+ transients.
Dave
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Division of Neurosurgery, Albany Medical College, NY 12208.
Vitarella
D
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Aschner
J L
JL
Fletcher
P
P
Kimelberg
H K
HK
Aschner
M
M
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007854:Lead / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*
D007854:Lead; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D009638:Norepinephrine