EFFECTS OF BETA-ODAP AND ITS BIOSYNTHETIC PRECURSOR ON THE ELECTROPHYSIOLOGICAL ACTIVITY OF CLONED GLUTAMATE RECEPTORS

3-N-Oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP) induces neurolathyr ism, a motor neuron disease. To elucidate the pathogenic mechanism of this process, the action of beta-ODAP on the excitatory amino acid (EA A) receptor-mediated currents was examined using cloned EAA receptors expressed in Xenopus oocytes. On the voltage-clamp recordings of an AM PA receptor(alpha(1)/alpha(2) heterooligomer), beta-ODAP was a strong agonist on this receptor, the potency being almost the same as L-gluta mate. On the other hand, beta-ODAP had little effect on the glutamate- evoked currents through the expressed NMDA receptor (NR1(A)/NR2A), but showed a weak inhibitory effect on the glycine-modulatory site. beta- ODAP may cause the neurodegenerative disease, neurolathyrism, mainly t hrough the excitotoxic interaction with AMPA receptors.