Dr. B. C. Seidman is Department of Neurology, UCSF School of Medicine, San Francisco, CA 94143, U.S.A.
Selective Inhibition of Synaptosomal γ-Aminobutyric Acid Uptake by Triethyllead: Role of Energy Transduction and Chloride Ion
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 48, Issue 4, pages 1142–1149, April 1987
How to Cite
Seidman, B. C. and Verity, M. A. (1987), Selective Inhibition of Synaptosomal γ-Aminobutyric Acid Uptake by Triethyllead: Role of Energy Transduction and Chloride Ion. Journal of Neurochemistry, 48: 1142–1149. doi: 10.1111/j.1471-4159.1987.tb05639.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Received June 9, 1986; revised October 6, 1986; accepted October 9, 1986
- γ-Aminobutyric acid;
- Synaptosomal uptake;
- Energy transduction;
- 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.