title: Neuropeptide S inhibits release of 5-HT and glycine in mouse amygdala and frontal/prefrontal cortex through activation of the neuropeptide S receptor.
abstract: 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 [(3)H]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 μM). NPS was an extremely potent inhibitor of the K(+)-evoked release of [(3)H]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.
authors: Department of Pharmacy, Pharmacology and Toxicology Unit, University of Genoa, Genoa, Italy.
authors: Elena
authors: E
authors: Gardella
authors: Cristina
authors: C
authors: Romei
authors: Anna
authors: A
authors: Cavallero
authors: Claudio
authors: C
authors: Trapella
authors: Ernesto
authors: E
authors: Fedele
authors: Luca
authors: L
authors: Raiteri
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D018013:Receptors, Neuropeptide; C583532:neuropeptide S receptor, mouse; C539972:neuropeptide S, mouse; D012701:Serotonin