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

Abstract

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 μM) or α-methyl- p-tyrosine (α-MPT) (1 mM), a tyrosine hydroxylase inhibitor reduced markedly each of these releases. NSD-1015 (20 μM), an aromatic l-amino acid decarboxylase inhibitor restored the inhibition by α-MPT of glutamate and DOPA but not DA release. DOPA cyclohexyl ester (DOPA CHE) (0.3–1 μM), 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 μM), an anticonvulsant or YM872 (1 μM), an α-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.