The neuropeptide S receptor (NPSR) is a member of the
G-protein coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
superfamily of
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a sign ...
s
which binds
neuropeptide S
Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other br ...
(NPS).
It was formerly an
orphan receptor
In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to ...
, 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
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
. 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
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
-like effects.
In addition, mututations in NPSR have been linked to a susceptibility to
asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
(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 metalloproteinase
Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...
s which are involved in the
pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
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, is found in human families that need less sleep time than normal ones. It has similar effects in transgenic mice, making them resistant to memory impairment caused by lack of sleep.
References
Further reading
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External links
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{{Neuropeptide receptors
G protein-coupled receptors