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 and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear.[10][11][12][13][14][15][16] It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway,[16] and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.[17]
Synthetic ligands[]
The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic.[18] Several peptide derived NPS agonists and antagonists have also been developed.[19][20][21][22][23]
Peptide sequence[]
Below are the sequences of mature neuropeptide S in several representative species in which it is expressed:
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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. PMID17099900. S2CID23864785.
^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. PMID16282594. S2CID30579961.
^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. ISBN978-3-540-78350-3. PMID18204825.
^Vitale G, Filaferro M, Ruggieri V, Pennella S, Frigeri C, Rizzi A, Guerrini R, Calò G (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. PMID18793688. S2CID207356961.
^ abMochizuki 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. PMID20156501. S2CID19981059.
^Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (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. PMID18181564.
^Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (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. PMID18793857.