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NPS receptor

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Target not currently curated in GtoImmuPdb

Target id: 302

Nomenclature: NPS receptor

Family: Neuropeptide S receptor

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 371 7p14.3 NPSR1 neuropeptide S receptor 1 26,39,76,90
Mouse 7 371 9 A3-A4 Npsr1 neuropeptide S receptor 1 55
Rat 7 372 8q13 Npsr1 neuropeptide S receptor 1
Previous and Unofficial Names Click here for help
VRR1 | GPR154 | PGR14 | G protein-coupled receptor 154 | vasopressin receptor-related receptor 1
Database Links Click here for help
Specialist databases
GPCRdb npsr1_human (Hs), npsr1_mouse (Mm), npsr1_rat (Rn)
Other databases
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
neuropeptide S {Sp: Human} , neuropeptide S {Sp: Mouse} , neuropeptide S {Sp: Rat}

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]Tyr10NPS (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.5 pKd 90
pKd 9.5 (Kd 3.3x10-10 M) [90]
PWT1-NPS Peptide Mm Full agonist 9.0 pEC50 73
pEC50 9.0 [73]
Description: In a calcium mobilisation assay
neuropeptide S {Sp: Mouse} Peptide Hs Full agonist 8.5 pEC50 90
pEC50 8.5 [90]
neuropeptide S {Sp: Rat} Peptide Hs Full agonist 8.5 pEC50 90
pEC50 8.5 [90]
neuropeptide S {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 7.3 – 8.0 pEC50 83,90
pEC50 8.0 [90]
pEC50 7.3 (EC50 4.6x10-8 M) [83]
Description: Agonist-induce intracellular Ca2+ mobilisation
NPS(1-4)NH2 Peptide Mm Full agonist 7.0 pEC50 12
pEC50 7.0 (EC50 1x10-7 M) [12]
Description: Measuring calcium mobilisation in cells expressing WT mNPS receptor (mNPSR-107I).
NPS(1-4)NH2 Peptide Hs Full agonist 6.0 pEC50 12
pEC50 6.0 (EC50 9.98x10-7 M) [12]
Description: Measuring calcium mobilisation in cells expressing WT hNPS receptor (hNPSR-107N).
[Cy5-Lys19]NPS Peptide Ligand is labelled Hs Full agonist 5.8 pEC50 46
pEC50 5.8 (EC50 1.5x10-6 M) [46]
View species-specific agonist tables
Agonist Comments
[125I]-Tyr10-hNPS = [125I]-Tyr10 Neuropeptide S (human).
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
NCGC 84 Small molecule or natural product Primary target of this compound Hs Antagonist 9.0 pA2 84
pA2 9.0 [84]
Description: Result from a cAMP accumulation assay.
SHA 68 Small molecule or natural product Mm Antagonist 8.1 pA2 74
pA2 8.1 [74]
SHA 68 Small molecule or natural product Rn Antagonist 7.6 pA2 72
pA2 7.6 [72]
[tBu-D-Gly5]NPS Peptide Rn Antagonist 7.2 pA2 72
pA2 7.2 [72]
[tBu-D-Gly5]NPS Peptide Mm Antagonist 7.1 pA2 25
pA2 7.1 [25]
[D-Cys(tBu)5]NPS Peptide Rn Antagonist 6.6 pA2 72
pA2 6.6 [72]
[D-Cys(tBu)5]NPS Peptide Mm Antagonist 6.4 pA2
pA2 6.4
[D-Val5]NPS Peptide Mm Antagonist 6.5 pKB 25
pKB 6.5 [25]
QA1 Small molecule or natural product Hs Antagonist 8.0 pIC50 51
pIC50 8.0 [51]
PI1 Small molecule or natural product Hs Antagonist 7.3 pIC50 86
pIC50 7.3 [86]
SHA 68R Small molecule or natural product Hs Antagonist 7.1 pIC50 83
pIC50 7.1 (IC50 8.64x10-8 M) [83]
Description: Antagonism of NPS-induced β-arrestin recruitment
RTI-118 Small molecule or natural product Hs Antagonist - - 92
[92]
Description: pKe value of 6.96 vs. hNPS receptor variant Ile107
View species-specific antagonist tables
Antagonist Comments
Antagonist SHA 68 has been tested against human Asn107 and Ile107 NPS receptor variants exhibiting pA2 values of 7.8 and 7.5 respectively [53].

The value for antagonist RTI-118 in the table above refers to human NPSR Ile107. The ligand has been tested also at the human NPSR Asn107 with pKe value of 6.31 [92].

NCGC 84 has also been tested in calcium mobilization and ERK phosphorylation assays where it displays pIC50 values of 7.44 and 8.03 respectively [84].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  4,82,90
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  26,64
Tissue Distribution Click here for help
Isoform B (377 amino acids) is found in apical epithelial cells in the bronchus and gut and in all layers of the epidermis.
Species:  Human
Technique:  Immunocytochemistry.
References:  39
Neuroendocrine tumours
Species:  Human
Technique:  Immunohistochemistry
References:  60
Pons: rostral laterodorsal tegmental nucleus, cuneiform nucleus, microcellular tegmental nucleus region, periaqueductal gray
Species:  Human
Technique:  In situ hybridization
References:  2
Isoform A (371 amino acids) is found in bronchial smooth muscle cells, basally in colon epithelium and in occasional basal keratinocytes in skin.
Species:  Human
Technique:  Immunocytochemistry.
References:  39
Brain: anterior olfactory nucleus, dorsal and ventral endopiriform nucleus, amygdala, precommissural nucleus, paraventricular thalamic nucleus, subiculum, motor cortex 2, retrosplenial agranular cortex, somatosensory cortex, hypothalamus, midbrain.
Species:  Mouse
Technique:  In situ hybridisation.
References:  11
Brain > salivary gland > thyroid, mammary gland > testis.
Species:  Rat
Technique:  RT-PCR.
References:  90
Brain: Hypothalamus > midbrain, forebrain > cortex, brainstem >hippocampus.
Species:  Rat
Technique:  RT-PCR.
References:  90
Brain: anterior olfactory nucleus, dorsal and ventral endopiriform nucleus, amygdala, precommissural nucleus, paraventricular thalamic nucleus, subiculum, motor cortex 2, retrosplenial agranular cortex, somatosensory cortex, hypothalamus, midbrain.
Species:  Rat
Technique:  in situ hybridisation.
References:  90
Brain: medial amygdala, substantia nigra pars compacta, subiculum, dorsal raphe, several hypothalamic and thalamic regions, pyramidal cell layer of the ventral hippocampus, medial habenula, cortex.
Species:  Rat
Technique:  Immunohistochemistry.
References:  44
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Stimulation of macrophage phagocytosis, adhesion and chemotaxis.
Species:  Mouse
Tissue:  Macrophage
Response measured:  Stimulation of phagocytosis, adhesion and chemotaxis.
References:  61
Stimulation of cAMP levels.
Species:  Human
Tissue:  HEK293 cells stably transfected with the human receptors
Response measured:  Increased levels of cAMP.
References:  46,64,84
Stimulation of BLA glutamatergic synaptic activity.
Species:  Mouse
Tissue:  Coronal brain slices.
Response measured:  Stimulation of glutamatergic transmission.
References:  33,50
Inhibition of K+ stimulated [3H]5-HT and [3H]NA release
Species:  Mouse
Tissue:  Frontal cortex synaptosomes.
Response measured:  Inhibition of [3H]5-HT and [3H]NA release.
References:  21,63
Increasing of Retinoid Acid Receptor-Related Orphan Receptor Alpha mRNA and related circadian clock genes
Species:  Human
Tissue:  Human SH-SY5Y cells stably transfected with the human receptor
Response measured:  Increased levels of Retinoid Acid Receptor-Related Orphan Receptor Alpha mRNA and related circadian clock genes
References:  1
Stimulation of ERK phosphorylation
Species:  Human
Tissue:  CHO or HEK293 cells transfected with the human NPS receptor
Response measured:  Increased levels of pERK 1/2
References:  46,84
Stimulation of intracellular calcium mobilization.
Species:  None
Tissue:  HEK293 cells stably transfected with the human, murine and rat NPS receptors.
Response measured:  Increased levels of intracellular calcium.
References:  4,18,64,72,82,90
Stimulation of dynamic mass redistribution.
Species:  Mouse
Tissue:  HEK293 cells transfected with the murine receptor.
Response measured:  Positive dynamic mass redistribution signal.
References:  70
Stimulation of intracellular calcium mobilization.
Species:  Rat
Tissue:  Brain slices from laterodorsal tegmentum, dorsal raphe, and centromedial thalamus.
Response measured:  Increased levels of intracellular calcium.
References:  67,89
Physiological Functions Click here for help
When injected centrally, NPS produces a long-lasting arousal, increasing locomotor activity.
Species:  Mouse
Tissue:  in vivo.
References:  9,66,90
When injected centrally, inhibits food intake. NB. This applies to rat AND mouse.
Species:  Rat
Tissue:  in vivo.
References:  19,57,80
When injected centrally, increases alcohol and cocaine seeking in reinstatement experiments. NB. This applies to rat AND mouse.
Species:  Rat
Tissue:  in vivo.
References:  8,34,56
When injected centrally, NPS promotes wakefulness and decreases both REM sleep and slow wave sleep. NB. This applies to rat AND mouse.
Species:  Rat
Tissue:  in vivo.
References:  10,37,66,90
When injected centrally, inhibits colonic transit.
Species:  Mouse
Tissue:  in vivo.
References:  27,88
When injected centrally, facilitates memory. This applies also to a murine Alzheimer's disease model.
Species:  Mouse
Tissue:  in vivo.
References:  28-30,52,77,93
Reduces anxiety- and panic-like behaviour when injected centrally and intranasally. NB. This applies to rat AND mouse.
Species:  Rat
Tissue:  in vivo.
References:  43,48,59,66,87,90-91
When injected centrally facilitates olfactory functions
Species:  Mouse
Tissue:  in vivo
References:  78
Facilitates the extinction of conditioned fear when injected centrally. NB. This applies to rat AND mouse.
Species:  Mouse
Tissue:  in vivo.
References:  33,75
When injected centrally reduces aggressiveness. NB. This applies to rat AND mouse.
Species:  Rat
Tissue:  in vivo
References:  3,69
When injected centrally and intranasally, produces antinociceptive effects.
Species:  Mouse
Tissue:  in vivo.
References:  31-32,40,45,49,58,65,91
When inject centrally, NPS ameliorates Parkinson’s disease related signs. NB. This applies to rat AND mouse.
Species:  Rat
Tissue:  In vivo.
References:  6,14,79
Physiological Consequences of Altering Gene Expression Click here for help
Mice with receptor knockout display increased anxiety levels.
Species:  Mouse
Tissue:  in vivo.
Technique:  Gene targeting in embryonic stem cells.
References:  17
Mice with receptor knockout display memory impairment.
Species:  Mouse
Tissue:  in vivo.
Technique:  Gene targeting in embryonic stem cells.
References:  52
Mice with receptor knockout displayed reduced sensitivity to the hypnotic effect of diazepam and EtOH
Species:  Mouse
Tissue: 
Technique:  Targeting in embryonic stem cells
References:  23
Mice with receptor knockout displayed decreased expression of Retinoid Acid Receptor-Related Orphan Receptor Alpha in the lung
Species:  Mouse
Tissue: 
Technique:  Targeting in embryonic stem cells
References:  1
Mice with receptor knockout display increased and generalized fear memory.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene targeting in embryonic stem cells.
References:  22,35
Mice with receptor knockout display increased aggressiveness levels
Species:  Mouse
Tissue:  In vivo
Technique:  Gene targeting in embryonic stem cells
References:  69
Mice with peptide precursor knockout display increased anxiety levels.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene targeting in embryonic stem cells.
References:  47
Mice with peptide precursor knockout display decreased locomotor activity.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene targeting in embryonic stem cells.
References:  47
Mice with peptide precursor knockout display impaired aversive memory.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene targeting in embryonic stem cells.
References:  47
Mice with peptide overexpression in the amygdala display reduced anxiety levels.
Species:  Mouse
Tissue:  In vivo.
Technique:  DNA delivery with recombinant adeno-associated viral vectors.
References:  85
Mice knock-in for the Y206H NPSR mutation display reduced sleep duration and reduced memory impairment after sleep deprivation.
Species:  Mouse
Tissue:  In vivo.
Technique:  CRISPR-Cas9
References:  89
Physiological Consequences of Altering Gene Expression Comments
NPS receptor knockout mice have been investigated in different laboratories. Of note, the anxious-like phenotype, the memory deficit and the reduced sensitivity to the hypnotic effect of diazepam and EtOH have not been replicated in other laboratories [7,20,71,94]. More importantly, the NPS stimulant [17,20,71,94] and arousal promoting [71] effects, the NPS anxiolytic-like [71,94] and anti-aggressiveness [69] actions are no longer evident in NPS receptor knockout mice.
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Npsr1tm1Bhk Npsr1tm1Bhk/Npsr1tm1Bhk
129S/SvEv-Npsr1
MGI:2441738  MP:0002328 abnormal airway resistance PMID: 16829631 
Npsr1tm1Bhk Npsr1tm1Bhk/Npsr1tm1Bhk
129S/SvEv-Npsr1
MGI:2441738  MP:0008872 abnormal physiological response to xenobiotic PMID: 16829631 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Asthma, susceptibility to, 2
Disease Ontology: DOID:2841
OMIM: 608584
Gene Expression and Pathophysiology Click here for help
The NPS receptor is significantly up-regulated in a mouse model of ovalbumen-induced lung inflammation
Tissue or cell type:  Lung
Pathophysiology:  Inflammation
Species:  Mouse
Technique: 
References:  39
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Y206H variant is associated with a short sleep phenotype.
Amino acid change:  Y206H
SNP accession: 
References:  89
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with decreased sleep- and rest duration
Amino acid change:  N107I
SNP accession: 
References:  81
Type:  Single nucleotide polymorphism
Species:  Human
Description:  An Asn107Ile variant is associated with susceptibility to inflammatory bowel disease.
Amino acid change:  N107I
SNP accession: 
References:  13
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with schizophrenia.
Amino acid change:  N107I
SNP accession: 
References:  42
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with enhanced response inhibition and increased error monitoring.
Amino acid change:  N107I
SNP accession: 
References:  5
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with panic disorders.
Amino acid change:  N107I
SNP accession: 
References:  15-16,54,62,68
Type:  Splice variants
Species:  Human
Description:  A splice variant (isoform B) with an alternative 3' exon, encoding a protein of 377 amino acids, is up-regulated in smooth muscle cells in asthmatic airways.
Amino acids:  377
Protein accession: 
References:  39
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with increased impulsivity and ADHD symptoms.
Amino acid change:  N107I
SNP accession: 
References:  38
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with a delay on bedtime.
Amino acid change:  N107I
SNP accession: 
References:  24
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with increased stress and cortisol levels
Amino acid change:  N107I
SNP accession: 
References:  36
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asn107Ile variant is associated with the early onset of obsessive-compulsive disorder
Amino acid change:  N107I
SNP accession: 
References:  41
General Comments
NPS precursor mRNA is highly expressed in a cluster of neurons located adjacent to the Locus coeruleus [90].

References

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1. Acevedo N, Sääf A, Söderhäll C, Melén E, Mandelin J, Pietras CO, Ezer S, Karisola P, Vendelin J, Gennäs GB et al.. (2013) Interaction between retinoid acid receptor-related orphan receptor alpha (RORA) and neuropeptide S receptor 1 (NPSR1) in asthma. PLoS ONE, 8 (4): e60111. [PMID:23565190]

2. Adori C, Barde S, Bogdanovic N, Uhlén M, Reinscheid RR, Kovacs GG, Hökfelt T. (2015) Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons. Front Neuroanat, 9: 126. [PMID:26441556]

3. Beiderbeck DI, Lukas M, Neumann ID. (2014) Anti-aggressive effects of neuropeptide S independent of anxiolysis in male rats. Front Behav Neurosci, 8: 185. [PMID:24910598]

4. Bernier V, Stocco R, Bogusky MJ, Joyce JG, Parachoniak C, Grenier K, Arget M, Mathieu MC, O'Neill GP, Slipetz D et al.. (2006) Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I. J Biol Chem, 281 (34): 24704-12. [PMID:16790440]

5. Beste C, Konrad C, Uhlmann C, Arolt V, Zwanzger P, Domschke K. (2013) Neuropeptide S receptor (NPSR1) gene variation modulates response inhibition and error monitoring. Neuroimage, 71: 1-9. [PMID:23319044]

6. Bülbül M, Sinen O, Özkan A, Aslan MA, Ağar A. (2019) Central neuropeptide-S treatment improves neurofunctions of 6-OHDA-induced Parkinsonian rats. Exp Neurol, 317: 78-86. [PMID:30825442]

7. Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, Guerrini R, Salvadori S, Reinscheid RK, Regoli D et al.. (2009) In vitro and in vivo pharmacological characterization of the neuropeptide s receptor antagonist [D-Cys(tBu)5]neuropeptide S. J Pharmacol Exp Ther, 328 (2): 549-55. [PMID:18971372]

8. Cannella N, Economidou D, Kallupi M, Stopponi S, Heilig M, Massi M, Ciccocioppo R. (2009) Persistent increase of alcohol-seeking evoked by neuropeptide S: an effect mediated by the hypothalamic hypocretin system. Neuropsychopharmacology, 34 (9): 2125-34. [PMID:19322167]

9. Castro AA, Moretti M, Casagrande TS, Martinello C, Petronilho F, Steckert AV, Guerrini R, Calo' G, Dal Pizzol F, Quevedo J et al.. (2009) Neuropeptide S produces hyperlocomotion and prevents oxidative stress damage in the mouse brain: a comparative study with amphetamine and diazepam. Pharmacol Biochem Behav, 91 (4): 636-42. [PMID:19022279]

10. Chauveau F, Claverie D, Lardant E, Varin C, Hardy E, Walter A, Canini F, Rouach N, Rancillac A. (2020) Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons. Sleep, 43 (1). [PMID:31403694]

11. Clark SD, Duangdao DM, Schulz S, Zhang L, Liu X, Xu YL, Reinscheid RK. (2011) Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry. J Comp Neurol, 519 (10): 1867-93. [PMID:21452235]

12. Clark SD, Kenakin TP, Gertz S, Hassler C, Gay EA, Langston TL, Reinscheid RK, Runyon SP. (2017) Identification of the first biased NPS receptor agonist that retains anxiolytic and memory promoting effects with reduced levels of locomotor stimulation. Neuropharmacology, 118: 69-78. [PMID:28267583]

13. D'Amato M, Bruce S, Bresso F, Zucchelli M, Ezer S, Pulkkinen V, Lindgren C, Astegiano M, Rizzetto M, Gionchetti P et al.. (2007) Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease. Gastroenterology, 133 (3): 808-17. [PMID:17854592]

14. Didonet JJ, Cavalcante JC, Souza Lde S, Costa MS, André E, Soares-Rachetti Vde P, Guerrini R, Calo' G, Gavioli EC. (2014) Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice. Behav Brain Res, 266: 29-36. [PMID:24613977]

15. Domschke K, Reif A, Weber H, Richter J, Hohoff C, Ohrmann P, Pedersen A, Bauer J, Suslow T, Kugel H et al.. (2011) Neuropeptide S receptor gene -- converging evidence for a role in panic disorder. Mol Psychiatry, 16 (9): 938-48. [PMID:20603625]

16. Donner J, Haapakoski R, Ezer S, Melén E, Pirkola S, Gratacòs M, Zucchelli M, Anedda F, Johansson LE, Söderhäll C et al.. (2010) Assessment of the neuropeptide S system in anxiety disorders. Biol Psychiatry, 68 (5): 474-83. [PMID:20705147]

17. Duangdao DM, Clark SD, Okamura N, Reinscheid RK. (2009) Behavioral phenotyping of neuropeptide S receptor knockout mice. Behav Brain Res, 205 (1): 1-9. [PMID:19646487]

18. Erdmann F, Kügler S, Blaesse P, Lange MD, Skryabin BV, Pape HC, Jüngling K. (2015) Neuronal expression of the human neuropeptide S receptor NPSR1 identifies NPS-induced calcium signaling pathways. PLoS ONE, 10 (2): e0117319. [PMID:25714705]

19. Fedeli A, Braconi S, Economidou D, Cannella N, Kallupi M, Guerrini R, Calò G, Cifani C, Massi M, Ciccocioppo R. (2009) The paraventricular nucleus of the hypothalamus is a neuroanatomical substrate for the inhibition of palatable food intake by neuropeptide S. Eur J Neurosci, 30 (8): 1594-602. [PMID:19821837]

20. Fendt M, Buchi M, Bürki H, Imobersteg S, Ricoux B, Suply T, Sailer AW. (2011) Neuropeptide S receptor deficiency modulates spontaneous locomotor activity and the acoustic startle response. Behav Brain Res, 217 (1): 1-9. [PMID:20888368]

21. Gardella E, Romei C, Cavallero A, Trapella C, Fedele E, Raiteri L. (2013) Neuropeptide S inhibits release of 5-HT and glycine in mouse amygdala and frontal/prefrontal cortex through activation of the neuropeptide S receptor. Neurochem Int, 62 (4): 360-6. [PMID:23411412]

22. Germer J, Kahl E, Fendt M. (2019) Memory generalization after one-trial contextual fear conditioning: Effects of sex and neuropeptide S receptor deficiency. Behav Brain Res, 361: 159-166. [PMID:30597251]

23. Ghazal P, Corsi M, Roth A, Faggioni F, Corti C, Merlo Pick E, Pucciarelli S, Ciccocioppo R, Ubaldi M. (2014) Paradoxical response to the sedative effects of diazepam and alcohol in C57BL/6J mice lacking the neuropeptide S receptor. Peptides, 61: 107-13. [PMID:25240770]

24. Gottlieb DJ, O'Connor GT, Wilk JB. (2007) Genome-wide association of sleep and circadian phenotypes. BMC Med Genet, 8 Suppl 1: S9. [PMID:17903308]

25. Guerrini R, Camarda V, Trapella C, Caló G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D et al.. (2009) Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists. J Med Chem, 52 (13): 4068-71. [PMID:19473027]

26. Gupte J, Cutler G, Chen JL, Tian H. (2004) Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach. Proc Natl Acad Sci USA, 101: 1508-1513. [PMID:14757815]

27. Han RW, Chang M, Peng YL, Qiao LY, Yin XQ, Li W, Wang R. (2009) Central Neuropeptide S inhibits distal colonic transit through activation of central Neuropeptide S receptor in mice. Peptides, 30 (7): 1313-7. [PMID:19540430]

28. Han RW, Xu HJ, Zhang RS, Wang P, Chang M, Peng YL, Deng KY, Wang R. (2014) Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation. Neurobiol Learn Mem, 107: 32-6. [PMID:24211255]

29. Han RW, Yin XQ, Chang M, Peng YL, Li W, Wang R. (2009) Neuropeptide S facilitates spatial memory and mitigates spatial memory impairment induced by N-methyl-D-aspartate receptor antagonist in mice. Neurosci Lett, 455 (1): 74-7. [PMID:19429110]

30. Han RW, Zhang RS, Xu HJ, Chang M, Peng YL, Wang R. (2013) Neuropeptide S enhances memory and mitigates memory impairment induced by MK801, scopolamine or Aβ₁₋₄₂ in mice novel object and object location recognition tasks. Neuropharmacology, 70: 261-7. [PMID:23454528]

31. Holanda AD, Asth L, Santos AR, Guerrini R, de P Soares-Rachetti V, Calo' G, André E, Gavioli EC. (2015) Central adenosine A1 and A2A receptors mediate the antinociceptive effects of neuropeptide S in the mouse formalin test. Life Sci, 120: 8-12. [PMID:25447449]

32. Holanda VAD, Oliveira MC, Souza LS, Lobão-Soares B, André E, Da Silva Junior ED, Guerrini R, Calo G, Ruzza C, Gavioli EC. (2019) Dopamine D1 and D2 receptors mediate neuropeptide S-induced antinociception in the mouse formalin test. Eur J Pharmacol, 859: 172557. [PMID:31326375]

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