共 74 条
Neuropeptide S inhibits release of 5-HT and glycine in mouse amygdala and frontal/prefrontal cortex through activation of the neuropeptide S receptor
被引:8
作者:
Gardella, Elena
[1
]
Romei, Cristina
[1
]
Cavallero, Anna
[2
]
Trapella, Claudio
[3
]
Fedele, Ernesto
[1
,4
]
Raiteri, Luca
[1
,4
,5
]
机构:
[1] Univ Genoa, Dept Pharm, Pharmacol & Toxicol Unit, Genoa, Italy
[2] CNR, Inst Biophys, Genoa, Italy
[3] Univ Ferrara, Dept Chem & Pharmaceut Sci, I-44100 Ferrara, Italy
[4] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy
[5] Natl Inst Neurosci, Genoa, Italy
关键词:
Neuropeptide S;
5-HT release;
Glycine release;
Amygdala;
Frontal/prefrontal cortex;
Anxiety;
NERVE-ENDINGS;
FOOD-INTAKE;
RAT-BRAIN;
IN-VIVO;
SHA;
68;
ANXIETY;
ANTAGONIST;
SYNAPTOSOMES;
SEROTONIN;
MECHANISMS;
D O I:
10.1016/j.neuint.2013.02.003
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:
Neuropeptide S (NPS) is a neurotransmitter/neuromodulator that has been identified as the natural ligand of G protein-coupled receptors termed NPS receptors (NPSRs). The NPS-NPSR system is involved in the control of numerous centrally-mediated behaviours, including anxiety. As several classical transmitters play a role in fear/anxiety, we here investigated the regulation by NPS of the exocytotic release of 5-hydroxytryptamine (5-HT) and glycine in nerve terminals isolated from mouse frontal/prefrontal cortex and amygdala. Synaptosomes, prelabelled with the tritiated neurotransmitters, were depolarized in superfusion with 12-15 mM KCl and exposed to varying concentrations of NPS. The evoked release of [H-3]5-HT in frontal/prefrontal cortex was potently inhibited by NPS (maximal effect about 25% at 0.1 nM). Differently, the neuropeptide exhibited higher efficacy but much lower potency in amygdala (maximal effect about 40% at 1 mu M). NPS was an extremely potent inhibitor of the K+-evoked release of [H-3]glycine in frontal/prefrontal nerve endings (maximal effect about 25% at 1 pM). All the inhibitory effects observed were counteracted by the NPSR antagonist SHA 68, indicating that the neuropeptide acted at NPSRs. In conclusion, NPS can inhibit the exocytosis of 5-HT and of glycine through the activation of presynaptic NPSRs situated on serotonergic and glycinergic terminals in areas involved in fear/anxiety behaviours. The possibility exists that the NPSRs in frontal/prefrontal cortex are high-affinity receptors involved in non-synaptic transmission, whereas the NPSRs on amygdala serotonergic terminals are low-affinity receptors involved in axo-axonic synaptic communication. (C) 2013 Elsevier Ltd. All rights reserved.
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页码:360 / 366
页数:7
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