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 microM) or alpha-methyl-p-tyrosine (alpha-MPT) (1 mM), a tyrosine hydroxylase inhibitor reduced markedly each of these releases. NSD-1015 (20 microM), 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 microM), 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 microM), an anticonvulsant or YM872 (1 microM), 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 inhibitory action on aglycemia-induced glutamate release among several neuroprotective agents tested.
Hashimoto
Mizuki
M
Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, 236-0004, Yokohama, Japan.
Miyamae
Takeaki
T
Yamamoto
Isao
I
Goshima
Yoshio
Y
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018696:Neuroprotective Agents; C110321:levodopa cyclohexyl ester; D018698:Glutamic Acid; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D005947:Glucose