title: Release of D,L-threo-beta-hydroxyaspartate as a false transmitter from excitatory amino acid-releasing nerve terminals.
abstract: This study examined whether preaccumulated D,L-threo-beta-hydroxyaspartate (tHA), a competitive substrate for the high-affinity excitatory amino acid (EAA) transporter, is released as a false transmitter from EAA-releasing nerve terminals. Potassium-stimulation (50 mM for 1 min) evoked significant release of the endogenous EAAs (aspartate and glutamate) from superfused neocortical minislices. Endogenous EAA release was largely calcium-dependent and was inhibited by tetanus toxin, a neurotoxin which specifically blocks vesicular exocytosis. In parallel experiments, minislices were pre-incubated with 500 microM tHA. Potassium (50 mM) evoked significant release of tHA and this release was also calcium-dependent and reduced by tetanus toxin. Pre-accumulation of tHA did not affect the release of endogenous glutamate whereas the release of endogenous aspartate was significantly attenuated. These data suggest that tHA selectively accumulates in a vesicular aspartate pool and is released upon depolarization as a false transmitter from EAA nerve terminals.
authors: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors: M W
authors: MW
authors: Fleck
authors: G
authors: G
authors: Barrionuevo
authors: A M
authors: AM
authors: Palmer
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018846:Excitatory Amino Acids / Q000378:metabolism*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission; D013744:Tetanus Toxin / Q000494:pharmacology
chemical_list: D018846:Excitatory Amino Acids; D013744:Tetanus Toxin; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid