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Original

The endogenous neurotransmitter, serotonin, modifies neuronal nitric oxide synthase activities

, , , , &
Pages 413-423 | Received 12 Jul 2006, Published online: 07 Jul 2009
 

Abstract

Serotonin, an important neurotransmitter, is colocalized with neuronal nitric oxide synthase (nNOS), a homodimeric enzyme which catalyzes the production of nitric oxide (NO) and/or oxygen species. As many interactions have been reported between the nitrergic and serotoninergic systems, we studied the effect of serotonin on nNOS activities. Our results reveal that nNOS is activated by serotonin as both NADPH consumption and oxyhemoglobin (OxyHb) oxidation were enhanced. The generation of l-citrulline from l-arginine (l-Arg) was not affected by serotonin in the range of 0–200 μM, suggesting an additional production of oxygen-derived species. But 5-hydroxytryptamine (5HT) induced the formation of both and H2O2 by nNOS, as evidenced by electron paramagnetic resonance (EPR) and by using specific spin traps. Overall, these results demonstrate that serotonin is able to activate nNOS, leading to the generation of reactive oxygen species (ROS) in addition to the NO production. Such a property must be considered in vivo as various nNOS-derived products mediate different signaling pathways.

Abbreviations
NO=

nitric oxide

nNOS=

neuronal nitric-oxide synthase

BH4=

6R-tetrahydrobiopterin

CaM=

calmodulin

5HT=

5-hydroxytryptamine or serotonin

DEPMPO=

5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide

BMPO=

5-tert-butyloxycarbonyl 5-methyl-1-pyrroline N-oxide

EPR=

electron paramagnetic resonance

SOD=

superoxide dismutase

OxyHb=

oxyhemoglobin

HPA=

4-hydroxyphenylacetic acid

NO2HPA=

4-hydroxy-3-nitrophenylacetic acid

Abbreviations
NO=

nitric oxide

nNOS=

neuronal nitric-oxide synthase

BH4=

6R-tetrahydrobiopterin

CaM=

calmodulin

5HT=

5-hydroxytryptamine or serotonin

DEPMPO=

5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide

BMPO=

5-tert-butyloxycarbonyl 5-methyl-1-pyrroline N-oxide

EPR=

electron paramagnetic resonance

SOD=

superoxide dismutase

OxyHb=

oxyhemoglobin

HPA=

4-hydroxyphenylacetic acid

NO2HPA=

4-hydroxy-3-nitrophenylacetic acid

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