The endogenous neurotransmitter, serotonin, modifies neuronal nitric oxide synthase activities.
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 microM, suggesting an additional production of oxygen-derived species. But 5-hydroxytryptamine (5HT) induced the formation of both O and H(2)O(2) 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.
Breard
Maud
M
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Avenue de la terrasse, Gif sur Yvette 91190, France.
Sari
Marie-Agnes
MA
Frapart
Yves
Y
Boucher
Jean-Luc
JL
Ducrocq
Claire
C
Grillon
Catherine
C
D000818:Animals; D001921:Brain / Q000378:metabolism; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D015971:Gene Expression Regulation, Enzymologic; D006861:Hydrogen Peroxide / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D012701:Serotonin / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D018377:Neurotransmitter Agents; D010108:Oxyhemoglobins; D017382:Reactive Oxygen Species; D013481:Superoxides; D002956:Citrulline; D012701:Serotonin; D009249:NADP; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III