Article date: 1987/8/1
PubMed ID: 3037027
Journal name: Journal of neurochemistry (ISSN: 0022-3042)
Triethyllead (TEL), the active metabolite of tetraethyllead, was shown previously to inhibit selectively high-affinity Na+-dependent uptake of gamma-aminobutyric acid (GABA) into cerebrocortical synaptosomes. Such inhibition was not related to the Na+ gradient, Na+,K+-ATPase activity, [Cl-], or energy charge. We report here that TEL inhibits GABA binding to the presynaptic transporter involved in Na+-dependent uptake. Scatchard plot analysis of Na+-dependent [3H]GABA binding to a highly purified synaptic plasma membrane preparation revealed that 25 microM TEL reduced the Bmax by 44%, leaving the KD unchanged. This binding was reversible and predominantly involved membrane uptake sites, as characterized by pharmacological specificity to GABA ligands. Approximately 85% of specific GABA binding was considered membrane uptake site binding, as indicated by sensitivity to nipecotic acid and diaminobutyric acid, with relative insensitivity to muscimol, bicuculline methiodide, baclofen, and beta-alanine. With respect to previous data, these finding suggest that TEL inhibits Na+-sensitive high-affinity GABA uptake by interfering with GABA binding to its presynaptic transporter.
Author List: Seidman B C, Olsen R W, Verity M A
Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Neurotoxins; Organometallic Compounds; Receptors, GABA-A; gamma-Aminobutyric Acid; triethyllead;
Mesh terms: Animals; Biological Transport/drug effects; Intracellular Membranes/metabolism; Kinetics; Neurotoxins/pharmacology; Organometallic Compounds/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Synaptosomes/metabolism; gamma-Aminobutyric Acid/metabolism;