Partial Involvement of Group I Metabotropic Glutamate Receptors in the Neurotoxicity of 3-N-Oxalyl-L-2,3-diaminopropanoic Acid (L-β-ODAP)

• Published in: Biological & pharmaceutical bulletin Vol. 27; no. 7; pp. 1052 - 1058
• Main Authors: Kusama-Eguchi, Kuniko, Kusama, Tadashi, Suda, Atsuhiro, Masuko, Takashi, Yamamoto, Makoto, Ikegami, Fumio, Igarashi, Kazuei, Kuo, Yu-Haey, Lambein, Fernand, Watanabe, Kazuko
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.07.2004; Japan Science and Technology Agency
• Subjects: 3-N-oxalyl-L-2,3-diaminopropanoic acid (L-β-ODAP); Amino Acids, Diamino - toxicity; Animals; Cells, Cultured; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - pharmacology; Female; metabotropic glutamate receptor; neurolathyrism; Neurotoxins - toxicity; primary cortical culture; Rats; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - physiology; Xenopus laevis; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.27.1052

Neurolathyrism is a human motoneuron disease caused by the overconsumption of grass pea (Lathyrus sativus) that contains a toxic non-protein amino acid, 3-N-oxalyl-L-2,3-diaminopropanoic acid (L-β-ODAP). The preventive activities of various glutamatergic agents from acute neuronal death caused by L-β-ODAP were studied using rat primary cortical neuron/glia culture. Nearly 80% of the rat primary cortical neurons were killed by 300 μM L-β-ODAP within 24 h. Though antagonists acting on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor prevented most of the toxicity, antagonists acting on group I metabotropic glutamatergic receptors (mGluRs), including (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), (S)-α-methyl-4-carboxyphenylglycine (MCPG), and 2-methyl-6-(2-phenylethenyl)pyridine (SIB1893) partially and significantly prevented neuronal death due to L-β-ODAP. These antagonists, within limited concentrations, did not have any inhibitory effects on the currents through AMPA receptors expressed in Xenopus oocytes. L-β-ODAP itself did not induce the currents through group I mGluRs expressed in Xenopus oocytes. These results suggest that the neurotoxicity induced by L-β-ODAP is partially mediated by the activation of group I mGluRs by an indirect mechanisms.