Identification | Back Directory | [Name]
NEUROPEPTIDE W-30 (HUMAN) | [CAS]
383415-80-3 | [Synonyms]
hL8 NPW PPL8 HL8C hPPL8 PPNPW NPW23 NPW30 HPPL8 (33-62) NPW30 (HUMAN) Neuropeptide W Preproprotein L8 Neuropeptide W-23 Neuropeptide W-30 NEUROPEPTIDE W-30 (HUMAN) PREPROPROTEIN L8 (33-62) (RAT) ANTI-NPW (C-TERM) antibody produced in rabbit Neuropeptide W-30 (human) trifluoroacetate salt NPW-30 (huMan), hPPL8 (33-62), Preproprotein L8 (33-62) (rat), hL8C Neuropeptide W-30 (huMan)
NPW-30 (huMan), hPPL8 (33-62), Preproprotein L8 (33-62) (rat), hL8C TRP-TYR-LYS-HIS-VAL-ALA-SER-PRO-ARG-TYR-HIS-THR-VAL-GLY-ARG-ALA-ALA-GLY-LEU-LEU-MET-GLY-LEU-ARG-SER-PRO-TYR-LEU-TRP TRP-TYR-LYS-HIS-VAL-ALA-SER-PRO-ARG-TYR-HIS-THR-VAL-GLY-ARG-ALA-ALA-GLY-LEU-LEU-MET-GLY-LEU-ARG-ARG-SER-PRO-TYR-LEU-TRP H-TRP-TYR-LYS-HIS-VAL-ALA-SER-PRO-ARG-TYR-HIS-THR-VAL-GLY-ARG-ALA-ALA-GLY-LEU-LEU-MET-GLY-LEU-ARG-ARG-SER-PRO-TYR-LEU-TRP-OH L-Tryptophan, L-tryptophyl-L-tyrosyl-L-lysyl-L-histidyl-L-valyl-L-alanyl-L-seryl-L-prolyl-L-arginyl-L-tyrosyl-L-histidyl-L-threonyl-L-valylglycyl-L-arginyl-L-alanyl-L-alanylglycyl-L-leucyl-L-leucyl-L-methionylglycyl-L-leucyl-L-arginyl-L-arginyl-L-seryl-L-prolyl-L-tyrosyl-L-leucyl- | [Molecular Formula]
C165H249N49O37S | [MDL Number]
MFCD06412271 | [MOL File]
383415-80-3.mol | [Molecular Weight]
3543.11 |
Questions And Answer | Back Directory | [Structure]
NPW cDNA encodes two forms of the peptide ligand
with lengths of 23 and 30 aa residues as mature peptides,
NPW23 and NPW30. These neuropeptides are derived
from a common precursor protein, proNPW, by the proteolytic processing of two pairs of arginine residues at
positions 24 and 25, and 31 and 32. Synthetic NPW23 activates and binds to two NPB/W receptors, NPBWR1
(GPR7) and NPBWR2 (GPR8), at similar effective doses. NPW precursor proteins are found in terrestrial vertebrate species, including mammals, birds, reptiles, and
amphibians. Human NPW23: Mr 2584.03; pI 10.28, Human NPW
30: Mr 3543.1; pI 11.0. Soluble in water. For best results,
rehydrate just before use. After rehydration, keep solution at + 4°C for up to 5 days or freeze at -20°C for up
to 3 months. | [Gene, mRNA, and precursor]
The gene encoding NPW maps to human chromosome
16p13.3. The gene encompasses 10.08 kb and is divided
into two exons. Human NPW mRNA is 751 bp long.
Among the porcine, rat, and human, the aa identities of
NPW23 and NPW30 are 91.3% and 90.0%, respectively. Based on RT-PCR analysis, NPW mRNA is highly
expressed in the substantia nigra and spinal cord, and
moderately expressed in the hippocampus, amygdala,
hypothalamus corpus callosum, cerebellum, and dorsal
root ganglia in the human central nervous system
(CNS). In the peripheral tissues of rodents, Npw mRNA
is expressed in the trachea, adrenocortical cells, gastric
antral G cells, thyroid and parathyroid glands, pancreatic
islets, ovary, and testis. | [Receptors]
Human NPBWR1 and NPBW2 genes are located on
chromosome 10q11.2–121.1 and 20q13.3, respectively.
Both receptors have 328 (36.1 kDa) and 333 (36.8 kDa)
aa residues, respectively, and share 64% sequence homology with each other.8 NPBWR1 orthologs are highly conserved among other mammalian species. In contrast, the
gene encoding NPBWR2 has not found in rodent
genomes, suggesting that these two receptors were produced by relatively phylogenetically recent gene
duplication. NPBWR1 and NPBWR2 couple to the Gi-class of
G-proteins but not the Gq-class, suggesting that NPW
has inhibitory properties on neurons via the activation
of GIRK (Kir3) channels. NPW stimulated the PKA,
PKC, p38 MAPK, and ERK1/2 activities in a dose- and
time-dependent manner via NPBWR1 in the ATDC5
cells. | [Biological functions]
In mammals, NPW regulates many physiological processes such as food intake, energy homeostasis, obesity,
neuroendocrine activity, and social behavior via its action
on the CNS. In addition to the CNS, NPW and its receptors are expressed in the peripheral tissues of rodents or
humans, such as the pancreas, stomach, adrenal cortex,
anterior pituitary, and adipocytes. NPW may be involved
in the control of adrenal corticosterone secretion, pancreatic insulin secretion, and lipolysis. Phenotype of gene-modified animals
NPW knockout mice behave abnormally in response
to life-threatening events (i.e., pain stimuli or a potential
predator) when the environment is novel and/or distracting. NPBWR1 knockout male mice show late-onset
obesity and hyperphagia, suggesting that the endogenous NPB/NPW-NPBWR1 pathway negatively regulates feeding behavior and positively regulates energy
expenditure. However, these phenotypic characteristics
are not observed in females. | [Clinical implications]
Direct linking between human diseases and the NPWNPBWR system has not been clarified yet. However,
NPBWR1 modulates feeding, metabolism, and obesity
in male mice. In humans, abdominal obesity is more prevalent in males, and is an independent risk factor for coronary heart disease. As activating or disrupting the
NPW-NPBWR1 system does not have pronounced effects
on growth and mortality in mice, NPBR1 and its ligand
may be helpful for the discovery of therapeutic drugs
and for designing therapies that overcome obesity and
other lifestyle-related disorders . | [Synthesis and release]
In the rat stomach, NPW is secreted in response to the
acute ingestion of a standard laboratory diet. Plasma
NPW concentrations in fasting rats are low, and increase
in response to feeding. Npw mRNA expression and the
number of NPW-positive cells in the mouse antrum
increase in diets including protein or glucose. |
Hazard Information | Back Directory | [Description]
The 23- or 30-aa neuropeptide identified as a ligand for
two orphan G-protein-coupled receptors (GPR7 and
GPR8), neuropeptide W (NPW) is involved in the regulation of feeding behavior and energy homeostasis via the neuronal circuits of the hypothalamus. O’Dowd et al. reported the existence of human
genes encoding two structurally related orphan
G protein-coupled receptors, NPBWR1 (GPR7) or
NPBWR2 (GPR8).1 However, the endogenous ligand
for these orphan receptors remained unknown until
2002. Shimomura et al. identified the mature peptide
sequences of neuropeptide B (NPB) and neuropeptide
W (NPW) from the porcine hypothalamus by reverse
pharmacology. |
|
|