Neuropeptides B/W receptor 1, also known as NPBW1 and GPR7, is a human
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
encoded by the NPBWR1
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
As implied by its name, it and related gene NPBW2 (with which it shares 70%
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
identity) are
transmembranes protein that bind
Neuropeptide B (NPB) and
Neuropeptide W (NPW), both proteins expressed strongly in parts of the brain that regulate stress and fear including the extended
amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verte ...
and
stria terminalis. When originally discovered in 1995, these receptors had no known
ligands ("orphan receptors") and were called GPR7 and GPR8, but at least three groups in the early 2000s independently identified their endogenous ligands, triggering the name change in 2005.
Structure
NPBW1 has seven
transmembrane domains
A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid b ...
, which it unsurprisingly shares with NPBWR2, but also a family of
somatostatin and
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
receptors, and like these proteins couple to Gi-class
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their a ...
s.
Functions
In rodent models, NPBWR1 is over-expressed in
Schwann cells
Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory en ...
associated with
neuropathic pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
, suggesting it inhibits inflammatory pain responses. Mice without NPBW1 exhibited a stronger hostile reaction to intruders, suggesting NPBW1 has a role in
stress responses. Early studies indicated that NPB and NPW had a complex effect on appetite, but generally led to
anorexia
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
. Similarly, male rats lacking NPBWR1 exhibited
hyperphagia
Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...
and adult-onset
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, though why female rats are unaffected is unknown. Researchers speculated that activating these pathways might decrease obesity, and synthesized a small-molecule ligand that is capable of stimulating both receptors at low concentrations.
[Romero F. A., Hastings N. B., Moningka R., Guo Z., Wang M., Di Salvo J., et al. (2012). The discovery of potent antagonists of NPBWR1 (GPR7). Bioorg. Med. Chem. Lett. 22, 1014–1018. doi:10.1016/j.bmcl.2011.11.126]
References
Further reading
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External links
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{{DEFAULTSORT:Neuropeptides B W receptor 1
G protein-coupled receptors