Neuropeptide S

Protein-coding gene in the species Homo sapiens

NPS

Identifiers
Aliases| NPS, neuropeptide S
External IDs| OMIM: 609513; MGI: 3642232; HomoloGene: 106066; GeneCards: NPS; OMA:NPS - orthologs
| Gene location (Human)

Chr.| Chromosome 10 (human)[1]

Band| 10q26.2| Start| 127,549,309 bp[1]
End| 127,553,540 bp[1]
| Gene location (Mouse)

Chr.| Chromosome 7 (mouse)[2]

Band| 7|7 F3| Start| 134,860,432 bp[2]
End| 134,874,671 bp[2]
| RNA expression pattern

Bgee| | Human| Mouse (ortholog)

|

| Top expressed in

* testicle

* islet of Langerhans

* prefrontal cortex

* substantia nigra

* Hypothalamus

* Temporal Lobe

* Amygdala

| Top expressed in

* embryo

* embryo

* spermatocyte

* testicle

* genital tubercle

* Hypothalamus

* cerebellar cortex

* spermatid

More reference expression data
BioGPS| | n/a

| Orthologs

Species| Human| Mouse
Entrez| |

594857

100043254

Ensembl| |

ENSG00000214285

ENSMUSG00000073804

UniProt| |

P0C0P6

P0C0P8

RefSeq (mRNA)| |

NM_001030013

NM_001163611

RefSeq (protein)| |

NP_001025184

NP_001157083

Location (UCSC)| Chr 10: 127.55 – 127.55 Mb| Chr 7: 134.86 – 134.87 Mb
PubMed search| [3]| [4]
Wikidata
| View/Edit Human| View/Edit Mouse

|

Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas.[5][6][7] NPS binds specifically to a G protein-coupled receptor, NPSR.[8][9] Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness[10] and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear.[11][12][13][14][15][16][17] It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway,[17] and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.[18]

## Synthetic ligands

[edit]

The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic.[19] Several peptide derived NPS agonists and antagonists have also been developed.[20][21][22][23][24]

## Peptide sequence

[edit]

Below are the sequences of mature neuropeptide S in several representative species in which it is expressed:

Protein family

| Neuropeptide S

Identifiers
Symbol| Neuropeptide_S
Pfam| PF14993
InterPro| IPR028138
| Available protein structures:

Pfam | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary
species  | sequence  | MW

|
|

human  | `SFRNGVGTGMKKTSFQRAKS` | 2187.5
rat  | `SFRNGVGSGVKKTSFRRAKQ` | 2210.5
mouse  | `SFRNGVGSGAKKTSFRRAKQ` | 2182.5
dog, chimp  | `SFRNGVGTGMKKTSFRRAKS` | 2215.6
chicken  | `SFRNGVGSGIKKTSFRRAKS` | 2183.5
consensus  | `SFRNGVGxGXKKTSFxRAKx` | N/A

According to Pfam's HMM logo, there is a conserved "KR" cleave site immediately N-terminal to the C-terminal mature peptide.

## References

[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000214285 - Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000073804 - Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Xu YL, Gall CM, Jackson VR, Civelli O, Reinscheid RK (Jan 2007). "Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain". The Journal of Comparative Neurology. 500 (1): 84–102\. doi:10.1002/cne.21159. PMID 17099900. S2CID 23864785.
6. ^ Jüngling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, et al. (Jul 2008). "Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala". Neuron. 59 (2): 298–310\. doi:10.1016/j.neuron.2008.07.002. PMC 2610688. PMID 18667157.
7. ^ Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T (2008). Grothe B (ed.). "Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus". PLOS ONE. 3 (7): e2695. Bibcode:2008PLoSO...3.2695M. doi:10.1371/journal.pone.0002695. PMC 2442874. PMID 18628994.
8. ^ Reinscheid RK, Xu YL (Dec 2005). "Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system". The Neuroscientist. 11 (6): 532–8\. doi:10.1177/1073858405276405. PMID 16282594. S2CID 30579961.
9. ^ Reinscheid RK (2008). "Neuropeptide S: Anatomy, Pharmacology, Genetics and Physiological Functions". Orphan G Protein-Coupled Receptors and Novel Neuropeptides. Results and Problems in Cell Differentiation. Vol. 46\. pp. 145–58\. doi:10.1007/400_2007_051. ISBN 978-3-540-78350-3. PMID 18204825.
10. ^ Chauveau F, Claverie D, Lardant E, Varin C, Hardy E, Walter A, et al. (January 2020). "Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons" (PDF). Sleep. 43 (1). doi:10.1093/sleep/zsz189. PMID 31403694.
11. ^ Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, et al. (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97\. doi:10.1016/j.neuron.2004.08.005. PMID 15312648. S2CID 15601843.
12. ^ Reinscheid RK, Xu YL (Nov 2005). "Neuropeptide S as a novel arousal promoting peptide transmitter". The FEBS Journal. 272 (22): 5689–93\. doi:10.1111/j.1742-4658.2005.04982.x. PMID 16279934. S2CID 42586325.
13. ^ Okamura N, Reinscheid RK (Aug 2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress. 10 (3): 221–6\. doi:10.1080/10253890701248673. PMID 17613937. S2CID 39068808.
14. ^ Leonard SK, Dwyer JM, Sukoff Rizzo SJ, Platt B, Logue SF, Neal SJ, et al. (May 2008). "Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders". Psychopharmacology. 197 (4): 601–11\. doi:10.1007/s00213-008-1080-4. PMID 18311561. S2CID 21120092.
15. ^ Rizzi A, Vergura R, Marzola G, Ruzza C, Guerrini R, Salvadori S, et al. (May 2008). "Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice". British Journal of Pharmacology. 154 (2): 471–9\. doi:10.1038/bjp.2008.96. PMC 2442439. PMID 18376418.
16. ^ Vitale G, Filaferro M, Ruggieri V, Pennella S, Frigeri C, Rizzi A, et al. (Dec 2008). "Anxiolytic-like effect of neuropeptide S in the rat defensive burying". Peptides. 29 (12): 2286–91\. doi:10.1016/j.peptides.2008.08.014. hdl:11380/610466. PMID 18793688. S2CID 207356961.
17. ^ a b Mochizuki T, Kim J, Sasaki K (May 2010). "Microinjection of neuropeptide S into the rat ventral tegmental area induces hyperactivity and increases extracellular levels of dopamine metabolites in the nucleus accumbens shell". Peptides. 31 (5): 926–31\. doi:10.1016/j.peptides.2010.02.006. PMID 20156501. S2CID 19981059.
18. ^ Wan Saudi WS, Halim MA, Rudholm-Feldreich T, Gillberg L, Rosenqvist E, Tengholm A, et al. (Oct 2015). "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol. 309 (9): G625-34. doi:10.1152/ajpgi.00104.2015. PMID 26206857. S2CID 5560949.
19. ^ Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK (Jun 2008). "Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor". The Journal of Pharmacology and Experimental Therapeutics. 325 (3): 893–901\. doi:10.1124/jpet.107.135103. PMC 2583099. PMID 18337476.
20. ^ Roth AL, Marzola E, Rizzi A, Arduin M, Trapella C, Corti C, et al. (Jul 2006). "Structure-activity studies on neuropeptide S: identification of the amino acid residues crucial for receptor activation" (PDF). The Journal of Biological Chemistry. 281 (30): 20809–16\. doi:10.1074/jbc.M601846200. PMID 16720571.
21. ^ Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, et al. (Feb 2008). "Synthesis and biological activity of human neuropeptide S analogues modified in position 2". Journal of Medicinal Chemistry. 51 (3): 655–8\. doi:10.1021/jm701204n. PMID 18181564.
22. ^ Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, et al. (Oct 2008). "Structure-activity study at positions 3 and 4 of human neuropeptide S". Bioorganic & Medicinal Chemistry. 16 (19): 8841–5\. doi:10.1016/j.bmc.2008.08.073. PMID 18793857.
23. ^ Guerrini R, Camarda V, Trapella C, Calò G, Rizzi A, Ruzza C, et al. (Jan 2009). "Synthesis and biological activity of human neuropeptide S analogues modified in position 5: identification of potent and pure neuropeptide S receptor antagonists". Journal of Medicinal Chemistry. 52 (2): 524–9\. doi:10.1021/jm8012294. PMC 2653091. PMID 19113861.
24. ^ Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, et al. (Feb 2009). "In vitro and in vivo pharmacological characterization of the neuropeptide s receptor antagonist [D-Cys(tBu)5]neuropeptide S". The Journal of Pharmacology and Experimental Therapeutics. 328 (2): 549–55\. doi:10.1124/jpet.108.143867. PMC 2630366. PMID 18971372.

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