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Keywords:

  • Triethyllead;
  • γ-Aminobutyric acid;
  • Synaptosomal uptake;
  • Energy transduction;
  • Cl;
  • Glutamate;
  • Ion modulation

Abstract: Triethyllead (TEL) is a CNS neurotoxin producing bizarre neurobehavioral changes. The principal objective of this study was to determine if TEL-induced defects in energy metabolism were responsible for the inhibition of synaptosomal Na+-dependent high-affinity uptake of γ-aminobutyric acid (GABA). A dose-dependent inhibition of GAB A uptake (ID50= 10 μMTEL) was found during 30-s incubations. Uptake of glutamate was more resistant to the inhibitory effects of TEL. A TEL-induced Cl -dependent synaptosomal deficit of ATP was observed. Such deficit in high-energy phosphate was time-dependent and did not occur in the absence of Cl or as early as 30 s. Inhibition of GABA uptake, on the other hand, was a Cl-independent phenomenon and was observed at as early as 30 s. TEL was not competitive with Na+ or GABA itself, as the effects of TEL were not overcome with high [Na+] or [GABA]. These results indicate that the locus of TEL inhibition of GABA uptake is not a Cl-dependent event and does not involve a perturbed transmembrane electrochemical gradient, due to either an observed mitochondrial defect or an inhibition of Na+, K+-ATPase directly.