Biology:Neuropeptide S

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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 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] and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.[13]

Synthetic ligands

The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic.[14] Several peptide derived NPS agonists and antagonists have also been developed.[15][16][17][18][19]

Peptide sequence

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

Neuropeptide S
Identifiers
SymbolNeuropeptide_S
PfamPF14993
InterProIPR028138
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

  1. ↑ "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. Jan 2007. doi:10.1002/cne.21159. PMID 17099900. 
  2. ↑ "Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala". Neuron 59 (2): 298–310. Jul 2008. doi:10.1016/j.neuron.2008.07.002. PMID 18667157. 
  3. ↑ Grothe, Benedikt, ed (2008). "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. PMID 18628994. Bibcode: 2008PLoSO...3.2695M.  open access
  4. ↑ "Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system". The Neuroscientist 11 (6): 532–8. Dec 2005. doi:10.1177/1073858405276405. PMID 16282594. 
  5. ↑ "Neuropeptide S: Anatomy, Pharmacology, Genetics and Physiological Functions". Orphan G Protein-Coupled Receptors and Novel Neuropeptides. Results and Problems in Cell Differentiation. 46. 2008. pp. 145–58. doi:10.1007/400_2007_051. ISBN 978-3-540-78350-3. 
  6. ↑ "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron 43 (4): 487–97. Aug 2004. doi:10.1016/j.neuron.2004.08.005. PMID 15312648. 
  7. ↑ "Neuropeptide S as a novel arousal promoting peptide transmitter". The FEBS Journal 272 (22): 5689–93. Nov 2005. doi:10.1111/j.1742-4658.2005.04982.x. PMID 16279934. 
  8. ↑ "Neuropeptide S: a novel modulator of stress and arousal". Stress 10 (3): 221–6. Aug 2007. doi:10.1080/10253890701248673. PMID 17613937. 
  9. ↑ "Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders". Psychopharmacology 197 (4): 601–11. May 2008. doi:10.1007/s00213-008-1080-4. PMID 18311561. 
  10. ↑ "Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice". British Journal of Pharmacology 154 (2): 471–9. May 2008. doi:10.1038/bjp.2008.96. PMID 18376418. 
  11. ↑ "Anxiolytic-like effect of neuropeptide S in the rat defensive burying". Peptides 29 (12): 2286–91. Dec 2008. doi:10.1016/j.peptides.2008.08.014. PMID 18793688. 
  12. ↑ 12.0 12.1 "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. May 2010. doi:10.1016/j.peptides.2010.02.006. PMID 20156501. 
  13. ↑ "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol 309 (9): G625-34. Oct 2015. doi:10.1152/ajpgi.00104.2015. PMID 26206857. 
  14. ↑ "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. Jun 2008. doi:10.1124/jpet.107.135103. PMID 18337476. 
  15. ↑ "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. Jul 2006. doi:10.1074/jbc.M601846200. PMID 16720571. 
  16. ↑ "Synthesis and biological activity of human neuropeptide S analogues modified in position 2". Journal of Medicinal Chemistry 51 (3): 655–8. Feb 2008. doi:10.1021/jm701204n. PMID 18181564. 
  17. ↑ "Structure-activity study at positions 3 and 4 of human neuropeptide S". Bioorganic & Medicinal Chemistry 16 (19): 8841–5. Oct 2008. doi:10.1016/j.bmc.2008.08.073. PMID 18793857. 
  18. ↑ "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. Jan 2009. doi:10.1021/jm8012294. PMID 19113861. 
  19. ↑ "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. Feb 2009. doi:10.1124/jpet.108.143867. PMID 18971372. 



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