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Research ArticleArticle

Dithiocarbamate Pesticides Affect Glutamate Transport in Brain Synaptic Vesicles

Andrea Vaccari, Pierluigi Saba, Ignazia Mocci and Stefania Ruiu
Journal of Pharmacology and Experimental Therapeutics January 1999, 288 (1) 1-5;
Andrea Vaccari
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Pierluigi Saba
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Ignazia Mocci
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Stefania Ruiu
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Abstract

Dithiocarbamate compounds are widely used agricultural fungicides that display low acute toxicity in mammals and that may become neurotoxic after prolonged exposure. Mancozeb, among other dithiocarbamates tested, proved to be the most potent (Ki= 0.27 μM) at noncompetitively inhibiting the in vitro ATP-dependent uptake of [3H]glutamate in rat cortical vesicles. Furthermore, mancozeb partially (20%) inhibited the ATP-dependent uptake of [14C]methylamine, used as an index for the vesicular transmembrane proton gradient (ΔpH), and evoked its efflux from organelles previously incubated with the3H-labeled marker. Meanwhile, the vesicular uptake of36chloride− anions whose concentrations regulate the transmembrane potential gradient (ΔψSV) was not impaired. The dithiocarbamate effects on the vesicular transport of [3H]glutamate thus appeared to involve mainly the ΔpH gradient rather than the potential gradient. Dithiocarbamate metabolites, the potent neurotoxin carbon disulfide included, did not affect the uptake process, thus implying the relevance for inhibition of the persistence, if any, of parent compounds in the brain. The present novel and potent in vitro interferences of selected dithiocarbamate pesticides with the vesicular transport of glutamate, if representative of in vivo alterations, may play some role in the probably complex origin of dithiocarbamate neurotoxicity.

Footnotes

  • Send reprint requests to: Prof. Andrea Vaccari, Department of Neuroscience, Via Porcell 4, 09124 Cagliari. E-mail address:avaccari{at}unica.it

  • ↵1 This work was supported by grants from the Regione Autonoma della Sardegna (Assessorato Difesa Ambiente, Contract 3680, 1993), and the Italian Ministry of Scientific and Technological Research (1995–1997) to A.V.

  • Abbreviations:
    DDTC
    diethyldithiocarbamic acid
    Δψsv
    potential gradient
    ΔpH
    proton gradient
    Cl
    chloride
    • Received March 12, 1998.
    • Accepted July 21, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 1
1 Jan 1999
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Research ArticleArticle

Dithiocarbamate Pesticides Affect Glutamate Transport in Brain Synaptic Vesicles

Andrea Vaccari, Pierluigi Saba, Ignazia Mocci and Stefania Ruiu
Journal of Pharmacology and Experimental Therapeutics January 1, 1999, 288 (1) 1-5;

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Research ArticleArticle

Dithiocarbamate Pesticides Affect Glutamate Transport in Brain Synaptic Vesicles

Andrea Vaccari, Pierluigi Saba, Ignazia Mocci and Stefania Ruiu
Journal of Pharmacology and Experimental Therapeutics January 1, 1999, 288 (1) 1-5;
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