The neuronal NOS inhibitor L-MIN, but not 7-NINA, reduces neurotoxic effects of chronic intrastriatal administration of quinolinic acid.
Rat striata were exposed to 15 mM quinolinic acid (QUIN), or QUIN plus the nitric oxide synthase inhibitors S-methyl-L-thiocitrulline dihydrochloride (L-MIN) or 7-nitroindazole monosodium salt (7-NINA) for 21 days. Co-administration of 100 microM or 1 mM L-MIN with QUIN significantly reduced lesion volume compared to QUIN alone. Co-administration of 1 microM or 10 microM L-MIN with QUIN had no significant effect. There was no significant effect of 7-NINA co-administered with QUIN compared to QUIN alone. L-MIN reduction of lesion volume supports the contention that neuronal nitric oxide synthase is a mediator of excitotoxic injury.
Bazzett
T
T
Department of Psychology, SUNY Geneseo 14454, USA. bazzett@uno.cc.geneseo.edu
Geiger
A
A
Coppola
B
B
Albin
R
R
D000818:Animals; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007191:Indazoles; D009498:Neurotoxins; D002956:Citrulline; D019001:Nitric Oxide Synthase; D017378:Quinolinic Acid; D013890:Thiourea; C086717:S-methylthiocitrulline; C080122:7-nitroindazole