Neuropeptide S

Neuropeptide S (NPS) was originally identified as the endogenous ligand of an orphan G-protein-coupled receptor (GRP154: NPSR) in 2004. NPS is a 20 amino acid peptide that is highly conserved among tetrapod vertebrates but is absent from fish genomes. The perfect conservation of the first seven amino acids (SFRNGVG) of NPS across all tetrapod species reflects the structural constraints for biological activity. NPS is involved in arousal, wakefulness, anxiolytic-like behaviors, fear, and learning and memory processes. These functions are regulated via two variants of NPSR. NPSR is functionally coupled with Gq and Gs, and its activation leads to the intracellular mobilization of Ca²⁺ and the formation of cAMP in cell line-expressed NPSR. NPS is related to the pathophysiology of a series of disorders such as generalized anxiety disorder (GAD), asthma, inflammatory bowel disease, and rheumatoid arthritis.