Neuropeptide S

Neuropeptide S
neuropeptide S
Symbol NPS
External IDs OMIM609513 MGI3642232 HomoloGene106066 GeneCards: NPS Gene
Species Human Mouse
Entrez 594857 100043254
Ensembl ENSG00000214285 ENSMUSG00000073804
UniProt P0C0P6 P0C0P8
RefSeq (mRNA) NM_001030013 XM_001479305
RefSeq (protein) NP_001025184 NP_001157083
Location (UCSC) Chr 10:
129.24 – 129.24 Mb
Chr 7:
142.46 – 142.46 Mb
PubMed search [1] [2]

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.[1][2][3] NPS binds specifically to a newly de-orphaned G protein-coupled receptor, NPSR.[4][5] Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear.[6][7][8][9][10][11][12] It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway.[12]

Synthetic ligands

The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic.[13] Several peptide derived NPS agonists and antagonists have also been developed.[14][15][16][17][18]

Peptide sequence

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

species sequence MW


  1. ^ Xu YL, Gall CM, Jackson VR, Civelli O, Reinscheid RK (January 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. 
  2. ^ Jüngling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, Okamura N, Duangdao DM, Xu YL, Reinscheid RK, Pape HC (July 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. 
  3. ^ Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T (2008). Grothe, Benedikt. ed. "Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus". PLoS ONE 3 (7): e2695. doi:10.1371/journal.pone.0002695. PMC 2442874. PMID 18628994. 
  4. ^ Reinscheid RK, Xu YL (December 2005). "Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system". The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry 11 (6): 532–8. doi:10.1177/1073858405276405. PMID 16282594. 
  5. ^ Reinscheid RK (2008). "Neuropeptide S: anatomy, pharmacology, genetics and physiological functions". Results and Problems in Cell Differentiation 46: 145–58. doi:10.1007/400_2007_051. PMID 18204825. 
  6. ^ Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (August 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. 
  7. ^ Reinscheid RK, Xu YL (November 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. 
  8. ^ Okamura N, Reinscheid RK (August 2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress (Amsterdam, Netherlands) 10 (3): 221–6. doi:10.1080/10253890701248673. PMID 17613937. 
  9. ^ Leonard SK, Dwyer JM, Sukoff Rizzo SJ, Platt B, Logue SF, Neal SJ, Malberg JE, Beyer CE, Schechter LE, Rosenzweig-Lipson S, Ring RH (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. 
  10. ^ Rizzi A, Vergura R, Marzola G, Ruzza C, Guerrini R, Salvadori S, Regoli D, Calo G (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. 
  11. ^ Vitale G, Filaferro M, Ruggieri V, Pennella S, Frigeri C, Rizzi A, Guerrini R, Calò G (December 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. PMID 18793688. 
  12. ^ a b Mochizuki T, Kim J, Sasaki K (February 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. 
  13. ^ Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK (June 2008). "Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-apyrazine-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. 
  14. ^ Roth AL, Marzola E, Rizzi A, Arduin M, Trapella C, Corti C, Vergura R, Martinelli P, Salvadori S, Regoli D, Corsi M, Cavanni P, Caló G, Guerrini R (July 2006). "Structure-activity studies on neuropeptide S: identification of the amino acid residues crucial for receptor activation". The Journal of Biological Chemistry 281 (30): 20809–16. doi:10.1074/jbc.M601846200. PMID 16720571. 
  15. ^ Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (February 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. 
  16. ^ Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (October 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. 
  17. ^ Guerrini R, Camarda V, Trapella C, Calò G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (January 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. 
  18. ^ Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, Guerrini R, Salvadori S, Reinscheid RK, Regoli D, Calò G (February 2009). "In vitro and in vivo pharmacological characterization of the neuropeptide s receptor antagonist [D-Cys(tBu)5neuropeptide 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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