Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7-nitro indazole.
The role of nitric oxide (NO) in striatal dopamine release has been controversial. Most NO synthase inhibitors affect more than one isoform of the enzyme and exert vasoconstrictor effects which may also affect striatal dopamine function. We now report on the effect of a soluble monosodium salt of the selective brain NO synthase inhibitor 7-nitro indazole (7-NINA). Using 7-NINA the first study of selective inhibition of the brain isoform of NO synthase on dopamine efflux in rat striatum was undertaken by use of in vivo microdialysis. Perfusion with 7-NINA (1 mM) increased striatal dopamine efflux. The effect of 7-NINA was partially antagonized (67%) by co-perfusion with L-arginine (1 mM), the precursor of NO formation in vivo. This suggests that 7-NINA induces a competitive inhibition of NO synthase activity. These data show that endogenous NO has an inhibitory effect on striatal dopamine efflux in vivo.
Silva
M T
MT
Neurodegenerative Diseases Research Centre, King's College London.
Rose
S
S
Hindmarsh
J G
JG
Aislaitner
G
G
Gorrod
J W
JW
Moore
P K
PK
Jenner
P
P
Marsden
C D
CD
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D007191:Indazoles; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C080122:7-nitroindazole; D004298:Dopamine