DOPA cyclohexyl ester potently inhibits aglycemia-induced release of glutamate in rat striatal slices

Brain ischemic insult causes glutamate release and resultant neuronal cell death. We here show that L-3,4-dihydroxyphenylalanine (DOPA) is a positive regulatory factor for glutamate release elicited by a mild brain insult using in vitro superfused rat striatal slices as a model system. Glucose deprivation for 18 min elicited release of glutamate, DOPA and dopamine (DA). Either tetrodotoxin (TTX) (1 muM) or alpha-methyl-p-tyrosine (alpha-MPT) (I mM), a tyrosine hydroxylase inhibitor reduced markedly each of these releases. NSD-1015 (20 muM), an aromatic L-amino acid decarboxylase inhibitor restored the inhibition by alpha-MPT of glutamate and DOPA but not DA release. DOPA cyclohexyl ester (DOPA CHE) (0.3-1 muM), a competitive DOPA antagonist, concentration-dependently suppressed aglycemia-induced glutamate release, the effect which was mimicked neither by S-sulpiride nor SCH23390, a DA D-1 or D-2 receptor antagonist, respectively. Zonisamide (1-1000 muM), an anticonvulsant or YM872 (1 muM), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) a receptor antagonist produced no effect on aglycemia-induced glutamate release. DOPA CHE thus showed a relatively potent inhibitiory action on aglycemia-induced glutamate release among several neuroprotective agents tested. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.