Neuropeptide S receptor

Template:Short description Template:Cs1 config Template:Infobox gene The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins which binds neuropeptide S (NPS). It was formerly an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Mutations in this gene have also been associated with this disease.

Clinical significance

In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic-like effects.

In addition, mututations in NPSR have been linked to a susceptibility to asthma (rs3249801, A107I). Hence NPSR has also been called GPRA (G protein-coupled receptor for asthma susceptibility). Activation of NPSR in the airway epithelium has a number of effects including upregulation of matrix metalloproteinases which are involved in the pathogenesis of asthma. It has been shown that activation of NPSR by NPS affects both gastrointestinal motility and mucosal permeability simultaneously. Aberrant signaling and upregulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions.

The very rare NPSR mutation Y206H, which makes the receptor more sensitive to NPS, may cause familial natural short sleep. This finding has not been investigated in animal models, and is sufficiently rare that a biobank study was unable to find other carriers to attempt a replication of the association with sleep duration.

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.