DOPA cyclohexyl ester, a competitive DOPA antagonist, protects glutamate release and resultant delayed neuron death by transient ischemia in hippocampus CA1 of conscious rats.
In rat striata, DOPA released is a causal factor for glutamate release and resultant delayed neuron death by four-vessel occlusion. Nanomolar DOPA cyclohexyl ester (CHE), a potent and relatively stable competitive DOPA antagonist, protects these events. We tried to clarify whether DOPA CHE protects these events in hippocampal CA1 pyramidal cell layers most vulnerable against ischemia. Five to 10 min ischemia caused slight to mild glutamate release in 10 min samples during microdialysis and mild to severe neuron death 96 h after reperfusion. DOPA and dopamine were under assay limit in this design, but were basally detected by 20 min sampling and released by 20 min ischemia. In 10 min samples, intrahippocampal perfusion of 100 nM DOPA CHE 10 min before ischemia for 70 min did not inhibit glutamate release by 10 min ischemia, while it abolished glutamate release and protected delayed neuron death by 5 min ischemia. DOPA CHE is neuroprotective under a mild ischemic condition in rat hippocampus CA1.
Arai
N
N
Department of Clinical Neuropathology, Tokyo Metropolitan Institute of Neuroscience, 183-8526, Tokyo, Japan.
Furukawa
N
N
Miyamae
T
T
Goshima
Y
Y
Sasaki
Y
Y
Ohshima
E
E
Suzuki
F
F
Fujita
K
K
Misu
Y
Y
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007980:Levodopa / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D018696:Neuroprotective Agents; C110321:levodopa cyclohexyl ester; D018698:Glutamic Acid; D007980:Levodopa; D004295:Dihydroxyphenylalanine