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Neuropeptide S receptor
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NPSR1
Identifiers
AliasesNPSR1, ASRT2, GPR154, GPRA, NPSR, PGR14, VRR1, neuropeptide S receptor 1
External IDsOMIM: 608595; MGI: 2441738; HomoloGene: 45515; GeneCards: NPSR1; OMA:NPSR1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_207173
NM_001300933
NM_001300934
NM_001300935
NM_207172

NM_175678

RefSeq (protein)

NP_001287862
NP_001287863
NP_001287864
NP_997055
NP_997056

NP_783609

Location (UCSC)Chr 7: 34.66 – 34.88 MbChr 9: 24.01 – 24.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins[5] which binds neuropeptide S (NPS).[6] 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.[7]

Clinical significance

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In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic-like effects.[8][9]

In addition, mututations in NPSR have been linked to a susceptibility to asthma (rs3249801, A107I).[10] 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.[11] 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.[12]

The very rare NPSR mutation Y206H, which makes the receptor more sensitive to NPS, may cause familial natural short sleep.[13] 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.[14]

References

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Further reading

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