TY - JOUR T1 - Structure-function studies on N-oxalyl-diamino-dicarboxylic acids and excitatory amino acid receptors: evidence that beta-L-ODAP is a selective non-NMDA agonist JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2073 LP - 2079 DO - 10.1523/JNEUROSCI.09-06-02073.1989 VL - 9 IS - 6 AU - RJ Bridges AU - DR Stevens AU - JS Kahle AU - PB Nunn AU - M Kadri AU - CW Cotman Y1 - 1989/06/01 UR - http://www.jneurosci.org/content/9/6/2073.abstract N2 - Excitatory amino acids and their receptors play an important role in both normal synaptic transmission and excitotoxic-mediated neuronal death. In the present investigation we have prepared a series of glutamate analogs and examined the pharmacological specificity with which they interact with excitatory amino acid receptors. Included within this group of compounds is a potent excitotoxic amino acid, beta- N-oxalyl-L-alpha, beta-diaminopropionic acid (beta-L-ODAP). This excitotoxin is of particular interest because it has been identified as a major causative agent of human neurolathyrism, a disease characterized by permanent spastic paralysis. The site of action of beta-L-ODAP was delineated with both electrophysiological recordings in hippocampal slices and radioligand binding assays in synaptic plasma membranes. We report that beta-L-ODAP is a potent agonist at the non-N- methyl-D-aspartate (NMDA) type of excitatory amino acid receptor. beta- L-ODAP interacts most potently with the quisqualate class of non-NMDA receptors (IC50 = 1.3 microM), less potently with the kainate receptor (IC50 = 17 microM), and very weakly with NMDA receptors. The specificity of this binding was consistent with physiological experiments that demonstrated that beta-L-ODAP-induced depolarizations were potently blocked by the newly identified non-NMDA receptor antagonist, CNQX, but were not affected by the NMDA antagonist D-AP5. These results extend recent studies that have focused on the contribution of NMDA receptors to excitotoxicity and highlight the potential involvement of non-NMDA receptors in excitotoxic-mediated cell death. ER -