Neuropeptide S (NPS) is a 20 amino acid neuropeptide that is processed from a larger precursor. NPS was named after a conserved serine residue at its N-terminus and is found in all tetrapod vertebrates but is absent from fish.
It is predominantly expressed in the central nervous system. The distribution pattern is only partially conserved between mice and rats. In both rat and mouse brain, expression of NPS precursor mRNA is found in the locus coeruleus (LC) area. In the parabrachial area, NPS precursor mRNA is expressed in the lateral parabrachial nucleus (LPB) in the rat brain, whereas expression in the mouse brain is found in the Kölliker-Fuse (KF) nucleus. Besides these two regions, NPS precursor mRNA is also found in additional regions in the rat brain, including the principal sensory trigeminal nucleus (Pr5).
NPS-responsive neurons extend projections into many other brain areas. NPS binds to its receptor NPSR1 to increase intracellular calcium concentrations. Physiologically, NPS has been characterized as a modulator of sleep/wake functions, locomotion, arousal/anxiety responses, food intake, and learning and memory.