Effects of organochlorine pesticides on 36Cl- flux in primary neuronal cultures.
Primary cultures from cortical neuronal cells were used to study the effect of organochlorine pesticides on GABA-dependent Cl- fluxes. In this system cyclodienes inhibited GABA-induced 36Cl- uptake with similar potencies to those described using brain synaptoneurosomes whereas lindane showed greater potency than that described using other in vitro systems. Basal Cl- uptake was not affected by these compounds although alpha-endosulfan exhibited a small inhibition. DDT, which mechanism of neurotoxic action has been postulated through activation of Na+ channels, did not inhibit GABA-induced 36Cl- uptake. These results clearly demonstrate that the stimulant neurotoxic effects of cyclodienes and lindane are produced by their interaction with the Cl- channel coupled to the GABAA receptor. Furthermore, these results show the usefulness of cortical neuronal cultures to study the effects of toxic agents on GABAA receptor.
Pomés
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Department of Neurochemistry, CID, Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
Rodríguez-Farré
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Suñol
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D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D003634:DDT / Q000633:toxicity; D005260:Female; D001556:Hexachlorocyclohexane / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D007306:Insecticides; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001556:Hexachlorocyclohexane; D003634:DDT