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Lindane cytotoxicity in cultured neocortical neurons is ameliorated by GABA and flunitrazepam
Author(s) -
Pomés A.,
Frandsen A. A.,
Suñol C.,
Sanfeliu C.,
RodríguezFarré E.,
Schousboe A.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490390606
Subject(s) - cytotoxicity , flunitrazepam , chemistry , pharmacology , lindane , neocortex , neuroscience , biology , benzodiazepine , biochemistry , ecology , pesticide , receptor , in vitro
The effect of lindane (γ‐hexachlorocyclohexane) on [ 35 S] t ‐butylbicyclophosphorothionate ([ 35 S]TBPS) binding and GABA‐stimulated 36 Cl − influx was investigated in cultured cerebral cortical neurons. In addition, the cytotoxic action of lindane as well as a protection by GABA and flunitrazepam were studied together with the ability of lindane to increase the intracellular concentration of free Ca 2+ . Lindane was found to be toxic to the neurons, an effect that could be completely prevented by the simultaneous presence of GABA (0.1 μM) and flunitrazepam (100 μM) and reduced by GABA alone. An interaction with the GABA receptor‐gated chloride channel was demonstrated by an inhibitory action of lindane on [ 35 S]TBPS binding (IC 50 188 ± 51 nM) and on GABA‐stimulated 36 Cl − influx in the neurons. Lindane only marginally increased the intracellular Ca 2+ concentration in the neurons. It is concluded that the cytotoxic action of lindane is mediated through interaction with GABA receptors in a manner essentially independent of changes in intracellular Ca 2+ homeostasis. © 1994 Wiley‐Liss, Inc.