Differential action of 7-nitro indazole on rat brain nitric oxide synthase.
We examined the dose-response characteristics of brain nitric oxide synthase (NOS) inhibition following intraperitoneal administration of 7-nitro indazole (7-NI). 7-NI inhibited striatal, hippocampal, cortical, cerebellar and nigral NOS activity in a dose-dependent manner. NOS activity in the striatum and hippocampus could not be inhibited more than 60% while cerebellar and nigral activity was depleted by at least 85%, indicating that 7-NI has differential effects in different brain regions. ED50 values obtained from the 7-NI dose-response curves of the striatum and hippocampus were significantly higher than the ED50 values obtained from the cortex, cerebellum and substantia nigra, further confirming the differential actions of 7-NI. In addition, inhibition of NOS activity 4.5 h following a maximal dose of 7-NI demonstrated differential recovery. At this time point, the cerebellum and hippocampus were more inhibited than the striatum, cortex and substantia nigra. Therefore, the extent of recovery from this inhibition was independent of the level of maximal NOS inhibition in the different brain regions. We suggest determining the extent and duration of NOS inhibition resulting from 7-NI administration prior to using it to study the role of neuronal nitric oxide (NO) in various systems.
Kalisch
B E
BE
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Connop
B P
BP
Jhamandas
K
K
Beninger
R J
RJ
Boegman
R J
RJ
D000818:Animals; D001921:Brain / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole