Effect of 7-nitro indazole on quinolinic acid-induced striatal toxicity in the rat.
Nitric oxide (NO) is implicated as a mediator of cell death in models of neurodegenerative disease. However, the precise role of NO in neuronal degeneration remains controversial. In the present study we employed 7-nitro indazole (7-NI), reportedly a selective inhibitor of neuronal nitric oxide synthase (nNOS) in vivo, to investigate the possible involvement of NO in quinolinic acid (QA)-induced striatal toxicity in the rat. Intrastriatal injection of QA (30 nmol) caused loss of NADPH diaphorase (48%), NOS (48%) and acetylcholinesterase (AChE; 22%) positive neurones and a loss of NOS activity (78%) in striatal homogenates. 7-NI (30 mg kg-1, i.p. every 4 h for 20 h) did not affect the loss of NADPH diaphorase (52%), NOS (52%) and AChE (16%) positive neurones or the loss of NOS activity (66%) in striatal homogenates. The present study does not support a role for NO in QA-induced striatal toxicity.
Neurodegenerative Diseases Research Centre, King's College London, UK.
G M
GM
MacKenzie
P
P
Jenner
C D
CD
Marsden
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007191:Indazoles; D009249:NADP; D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase; D017378:Quinolinic Acid; C080122:7-nitroindazole