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- Title
Activity of the enantiomers of erythro-3-hydroxyaspartate at glutamate transporters and NMDA receptors.
- Authors
Foster, Alan C.; Li, Yong‐Xin; Runyan, Stephen; Dinh, Tim; Venadas, Steven; Chen, June; Pashikanti, Srinath; Datta, Apurba; Ehring, George; Staubli, Ursula
- Abstract
The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters and NMDA receptors. Both enantiomers inhibited glutamate transporters in rat hippocampal crude synaptosomes and elicited substrate-like activity at excitatory amino acid transporter 1, 2, and 3 as measured by voltage clamp in the Xenopus oocyte expression system. The enantiomers had similar affinities, but the D-enantiomer showed a lower maximal effect at excitatory amino acid transporter 1, 2, and 3 than the L-enantiomer. Surprisingly, D-erythro-3-hydroxyaspartate was a potent NMDA receptor agonist with an EC50 value in rat hippocampal neurons of 320 nM, whereas the L-enantiomer was 100-fold less potent. L-erythro-3-hydroxyaspartate showed activity at both glutamate transporters and NMDA receptors at concentrations that are reported to inhibit serine racemase, indicating a lack of selectivity. This enantiomeric pair may assist in shedding further light on the structural requirements for substrate activity at glutamate transporters and for agonist activity at NMDA receptors.
- Subjects
ENANTIOMERS; GLUTAMATE transporters; METHYL aspartate receptors; RACEMASES; AMINO acid transport; VOLTAGE-clamp techniques (Electrophysiology); GENE expression
- Publication
Journal of Neurochemistry, 2016, Vol 136, Issue 4, p692
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.13430