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

被引:12
作者
Breard, Maud
Sari, Marie-Agnes
Frapart, Yves
Boucher, Jean-Luc
Ducrocq, Claire
Grillon, Catherine
机构
[1] CNRS, Inst Chim Subst Nat, F-91190 Gif Sur Yvette, France
[2] Univ Paris 05, Chim & Biochim Pharmacol & Toxicol Lab, F-75005 Paris, France
关键词
neuronal nitric oxide synthase; reactive oxygen species; superoxide; hydrogen peroxide; serotonin; neurotransmitter; HYDROGEN-PEROXIDE; TRYPTOPHAN-HYDROXYLASE; SUPEROXIDE GENERATION; SPIN TRAPS; PEROXYNITRITE; TETRAHYDROBIOPTERIN; INACTIVATION; BRAIN; INHIBITION; MECHANISM;
D O I
10.1080/10715760601105681
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Serotonin, an important neurotransmitter, is colocalized with neuronal nitric oxide synthase (nNOS), a homodimeric enzyme which catalyzes the production of nitric oxide (NO center dot) 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 mu M, suggesting an additional production of oxygen-derived species. But 5-hydroxytryptamine (5HT) induced the formation of both O-2(center dot-) 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 center dot production. Such a property must be considered in vivo as various nNOS-derived products mediate different signaling pathways.
引用
收藏
页码:413 / 423
页数:11
相关论文
共 44 条
[11]  
Ishida Tatsuro, 1998, Kobe Journal of Medical Sciences, V44, P51
[12]   Morphological relationship between serotonergic neurons and nitrergic neurons for electrolytes secretion in the submucous plexus of the guinea pig distal colon [J].
Kadowaki, M ;
Kuramoto, H ;
Kuwahara, A .
BRAIN RESEARCH, 1999, 831 (1-2) :288-291
[13]  
Kelm M, 1997, J BIOL CHEM, V272, P9922
[14]   Comparative investigation of superoxide trapping by cyclic nitrone spin traps: The use of singular value decomposition and multiple linear regression analysis [J].
Keszler, A ;
Kalyanaraman, B ;
Hogg, N .
FREE RADICAL BIOLOGY AND MEDICINE, 2003, 35 (09) :1149-1157
[15]   Formation and properties of peroxynitrite as studied by laser flash photolysis, high-pressure stopped-flow technique, and pulse radiolysis [J].
Kissner, R ;
Nauser, T ;
Bugnon, P ;
Lye, PG ;
Koppenol, WH .
CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (11) :1285-1292
[16]   Autoinhibition of neuronal nitric oxide synthase:: distinct effects of reactive nitrogen and oxygen species on enzyme activity [J].
Kotsonis, P ;
Frey, A ;
Fröhlich, LG ;
Hofmann, H ;
Reif, A ;
Wink, DA ;
Feelisch, M ;
Schmidt, HHHW .
BIOCHEMICAL JOURNAL, 1999, 340 :745-752
[17]  
Kuhn DM, 1997, J NEUROCHEM, V68, P1495
[18]  
Kuhn DM, 1996, J NEUROCHEM, V67, P1072
[19]   Structure-related inhibition of calmodulin-dependent neuronal nitric-oxide synthase activity by melatonin and synthetic kynurenines [J].
León, J ;
Macías, M ;
Escames, G ;
Camacho, E ;
Khaldy, H ;
Martín, M ;
Espinosa, A ;
Gallo, MA ;
Acuña-Castroviejo, D .
MOLECULAR PHARMACOLOGY, 2000, 58 (05) :967-975
[20]   Role of paraquat in the uncoupling of nitric oxide synthase [J].
Margolis, AS ;
Porasuphatana, S ;
Rosen, GM .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2000, 1524 (2-3) :253-257