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[The effect of triorthocresyl phosphate on the toxicity of GABA-lytics for mice]

A I Golovko, G A Sofronov, T V Nikolaeva

    Biulleten' Eksperimental'Noi Biologii I Meditsiny
    |October 1, 1993
    PubMed

    Insights

    Triorthocresyl phosphate (TOCP) increased the toxicity of certain GABA receptor antagonists in mice. This neurotoxic effect may involve altered GABA receptor affinity and inhibited blood carboxylesterases.

    Area of Science:

    • Neuroscience
    • Toxicology
    • Pharmacology

    Background:

    • Triorthocresyl phosphate (TOCP) is an organophosphate known for its neurotoxic effects.
    • GABA receptors are crucial inhibitory neurotransmitter receptors in the central nervous system.

    Purpose of the Study:

    • To investigate the effect of TOCP pretreatment on the toxicity of GABA antagonists.
    • To explore the underlying mechanisms of TOCP-induced neurotoxicity related to GABAergic neurotransmission.

    Main Methods:

    • Mice were pretreated with TOCP.
    • Toxicity of bicuculline and 3-mercaptopropionic acid was assessed.
    • Binding affinity of brain GABA receptors for [3H] GABA and [3H]-t-butylcycloorthobenzoate was measured.

    Main Results:

    • TOCP pretreatment significantly increased the toxicity of bicuculline, a picrotoxin.
    • TOCP did not alter the toxicity of 3-mercaptopropionic acid.
    • TOCP decreased the binding affinity of brain GABA receptors for [3H] GABA.
    • Binding of [3H]-t-butylcycloorthobenzoate to receptors was unaffected.

    Conclusions:

    • Increased toxicity of GABA antagonists following TOCP exposure may be linked to inhibited blood carboxylesterases.
    • A direct influence of TOCP or its metabolites on the GABA/benzodiazepine receptor complex is possible.

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