Differential effects of inorganic lead and delta-aminolevulinic acid in vitro on synaptosomal gamma-aminobutyric acid release.
Several studies have shown that inorganic lead added in vitro does not alter gamma-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 delta-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 microM) 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 AT-Pase. ALA also induces a dose-dependent [3H]GABA release, but only at concentrations equal to or greater than 30 microM. Exposure to a combination of 3 microM lead and 100 microM 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 microM), whereas ALA (30-300 microM) 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.
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D007982:Levulinic Acids / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007982:Levulinic Acids; D007854:Lead; D005680:gamma-Aminobutyric Acid; D000622:Aminolevulinic Acid