Neuropeptide S (NPS)

Neuropeptide S is a 20-amino acid peptide neurotransmitter that acts as the endogenous ligand for the Neuropeptide S receptor (NPSR), a G protein-coupled receptor. NPS is expressed primarily in a restricted neuronal population in the brainstem (especially near the locus coeruleus), while its receptor is widely expressed throughout the CNS (including the amygdala, subiculum, cortex), and peripherally in tissues such as the airway epithelium. NPS signaling promotes arousal, enhances memory during the consolidation phase, reduces anxiety, and modulates fear extinction. Polymorphisms in NPSR are clinically linked to roles in asthma, anxiety disorders, and rare sleep syndromes. Pharmacologic manipulation of NPSR is under investigation for potential treatments of anxiety, cognitive dysfunction, and inflammatory conditions.

Other names

Neuropeptide SNPSprepro-neuropeptide S

NPS activates NPSR, a G protein-coupled receptor, promoting cAMP signaling, Ca²⁺ mobilization, and neurotransmitter release (including enhanced glutamatergic transmission). NPSR antagonists block receptor function and consequently NPS-mediated effects.