Differential effects of inorganic lead and δ-aminolevulinic acid in vitro on synaptosomal γ-aminobutyric acid release,☆☆

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Abstract

Several studies have shown that inorganic lead added in vitro does not alter γ-aminobutyric acid (GABA) release from rat brain synaptosomes. The decrease in GABA release observed following chronic neonatal in vivo lead exposure has been proposed to be an indirect effect mediated by the increase in δ-aminolevulinic acid (ALA) accompanying chronic lead exposure. In the present study the effect of both lead and ALA in vitro on several aspects of [3H]GABA release from superfused rat cortical synaptosomes are examined. The present study demonstrates that lead (1–30 μm) added in vitro induces [3H]GABA release from preloaded cortical synaptosomes in a dose-dependent manner. This lead-induced increase in spontaneous [3H]GABA release does not appear to be mediated by inhibition of the membrane Na-K ATPase. ALA also induces a dose-dependent [3H]GABA release, but only at concentrations equal to or greater than 30 μm. Exposure to a combination of 3 μm lead and 100 μm ALA results in an increase in spontaneous [3H]GABA release that is greater than either treatment separately. The depolarization-evoked release of [3H]GABA resulting from a 1-sec exposure to 61 mm potassium chloride is reduced by lead (3 and 10 μm), whereas ALA (30–300 μm) does not alter depolarization-evoked release. These findings indicate that an indirect action of lead (elevated ALA concentrations) need not be proposed to explain the alterations in GABA release observed following chronic lead exposure.

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  • Cited by (0)

    Supported by NIH-NIEHS-03399.

    ☆☆

    A preliminary report was presented at the 25th annual meeting of the Society of Toxicology, New Orleans, La., March 1986.

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