TY - JOUR
T1 - Lead increases inositol 1,4,5-triphosphate levels but does not interfere with calcium transients in primary rat astrocytes
AU - Dave, Vijendra
AU - Vitarella, Domenico
AU - Aschner, Judy L.
AU - Fletcher, Paul
AU - Kimelberg, Harold K.
AU - Aschner, Michael
N1 - Funding Information:
Acknowledgments. The authors wish to thank Paige A. Conley and Carol Charniga for their technical assistance, and the Upjohn Co., Kalamazoo, MI, for their kind gift of U73122. The research described herein was partially supported by grants from the NIH ES05223 and EPA R81910 awarded to M.A., and NIH NS 23750 awarded to H.K.K.J.L.A. was supported in part by the Parker B. Francis Fellowship Foundation. The Deltascan was purchased by a Small Instrumentation Grant from the NIH HL 44035 awarded to the Albany Medical College.
PY - 1993/7/30
Y1 - 1993/7/30
N2 - 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 Ca2+-mediated cellular processes, we analyzed the effect of Pb exposure on α1 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 μM) 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 μM 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 μM). 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.
AB - 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 Ca2+-mediated cellular processes, we analyzed the effect of Pb exposure on α1 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 μM) 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 μM 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 μM). 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.
KW - Astrocyte
KW - Calcium
KW - Inositol polyphosphate
KW - Lead
KW - Norepinephrine
KW - Phospholipase C
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U2 - 10.1016/0006-8993(93)90422-J
DO - 10.1016/0006-8993(93)90422-J
M3 - Article
C2 - 8402182
AN - SCOPUS:0027317818
SN - 0006-8993
VL - 618
SP - 9
EP - 18
JO - Brain research
JF - Brain research
IS - 1
ER -