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Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells

WW Lin, JG Kiang and DM Chuang
Journal of Neuroscience 1 March 1992, 12 (3) 1077-1085; DOI: https://doi.org/10.1523/JNEUROSCI.12-03-01077.1992
WW Lin
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
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JG Kiang
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
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DM Chuang
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
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Abstract

Because increasing evidence indicates that glial cells are a target of endothelin, we have characterized endothelin-induced phosphoinositide (PI) turnover and Ca2+ homeostasis in C6 glioma cells. Endothelin-1 (ET) increased formation of 3H-inositol phosphate (IP) from PI and elicited an increase in cytosolic free Ca2+ ([Ca2+]i) in rat C6 glioma. In the presence of Li+, the increase in 3H-inositol trisphosphate formation was rapid, reaching its peak at 5 min after stimulation. ET also elicited a rapid and sustained increase in [Ca2+]i in a dose- dependent manner (1–100 nM). The rank orders of efficacy for ET-related peptides in increasing [Ca2+]i were ET = ET-2 greater than sarafotoxin greater than ET-3. Both ET-mediated stimulation of IP formation and [Ca2+]i increase were largely inhibited in the absence of external Ca2+ but unaffected by the depletion of external Na+ and the presence of dihydropyridine derivatives or verapamil. Inorganic Ca2+ channel blockers Cd2+, La3+, and Mn2+ at 1 mM inhibited both responses induced by ET. Cross-desensitization and nonadditivity were observed for both events among ET-related peptides tested, but not between ET and ATP. Pretreatment of cells with pertussis toxin (PTX) attenuated the PI response to ET, but had no effect on ET-elicited [Ca2+]i increase. ET- induced Ca2+ mobilization (measured in Ca(2+)-free medium) was only transient and was inhibited by 8-(N,N-diethylamino)octyl-3,4,5- trimethoxybenzoate. Moreover, the intracellular Ca2+ pools mobilized by ET and ATP appeared to overlap, as indicated by their partial heterologous desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Journal of Neuroscience: 12 (3)
Journal of Neuroscience
Vol. 12, Issue 3
1 Mar 1992
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Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells
WW Lin, JG Kiang, DM Chuang
Journal of Neuroscience 1 March 1992, 12 (3) 1077-1085; DOI: 10.1523/JNEUROSCI.12-03-01077.1992

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Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells
WW Lin, JG Kiang, DM Chuang
Journal of Neuroscience 1 March 1992, 12 (3) 1077-1085; DOI: 10.1523/JNEUROSCI.12-03-01077.1992
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