| Neuropeptide W | |||||||
|---|---|---|---|---|---|---|---|
 Neuropeptide W primary sequence using three letters code. N-terminal represented in blue. C-terminal represented in red. | |||||||
| Identifiers | |||||||
| Symbol | ? | ||||||
| UniProt | Q8N729 | ||||||
| Other data | |||||||
| Wikidata | Q21173201 | ||||||
| |||||||
Neuropeptide W or preprotein L8 is a short human neuropeptide. [1] Neuropeptide W acts as a ligand for two neuropeptide B/W receptors, NPBWR1 and NPBWR2, which are integrated in GPCRs family of alpha-helical transmembrane proteins. [2] [3]
There are two forms of neuropeptide W whose precursor is encoded by NPW gene. [4]
The 23-amino-acid form (neuropeptide W-23) is the one that activates the receptors whereas the C-terminally extended form (neuropeptide W-30) is less effective. These isoforms were demonstrated in different species like rat, human, chicken, mouse and pig. [5]
The name of neuropeptid W is due to the tryptophan residues located on both sides, the N- side and -C side, in its two mature forms.
Neuropeptide W was first identified in porcine hypothalamus in 2002. [6] In humans, it is highly confined in neurons of the substantia nigra and the spinal cord, and fewer expressed in neurons of the hippocampus, hypothalamus, amygdala, parietal cortex and cerebellum. [7] It can also be found in some peripheral tissues such as trachea, stomach, liver, kidney prostate, uterus and ovary. It has to be said that tissue distribution information is still lacking. [8] For the moment, Neuropeptide W location differences between studied species (rat, mouse, chicken, pig) are slight, even though quantities differ between the organs. [9]
Neuropeptide W in the Central Nervous System is surely implicated in feeding activity and energy metabolism, in the adrenal axis stress response, and the regulation of neuroendocrine functions like the hormone release from the pituitary gland, but it is not considered as an inhibitory or regulatory factor in it. Neuropeptide W may also be involved in autonomic regulation, pain sensation, emotions, anxiety and fear. [10] [11]
It seems that regulation of feeding behaviour and energy metabolism is the primary function of the neuropeptide W signaling system. On the one hand, Neuropeptide W regulates the endocrine signals aimed at anterior hypophysis. This stimulates both the need for water (thirst) and the need for food (hunger). On the other hand, it plays a compensatory role in energy metabolism. [12]
Regarding the adrenal axis response to stress, it plays a relevant role as a messenger in brain networks that help the activation of HPA (hypothalamic–pituitary–adrenal axis), which will cause the response to stress. [9]
An example of neuroendocrine functions is the regulation of the secretion of cortisol due to the activation or deactivation of neuropeptide B/W receptors. [13] [14]
Moreover, Neuropeptide W is found in an area that is connected with preauthonomic centers in the brainstem and spinal cord. Because of this location, there is a chance that it can affect some cardiovascular function. [15]
Infusion of neuropeptide W has been shown to suppress the eating of food and body weight and increase heat production and body temperature, this verifies its works as an endogenous catabolic signaling molecule. [1]
Nevertheless, function and physiological role of peripheric neuropeptid W is not clearly known.
Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol by the cortex of the adrenal gland. ACTH is also related to the circadian rhythm in many organisms.
Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation. POMC is part of the central melanocortin system.
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the mammalian central nervous system, which consists of the brain and spinal cord. It is secreted alongside other neurotransmitters such as GABA and glutamate.
Beta-Endorphin or β-Endorphin is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.
Kisspeptins are proteins encoded by the KISS1 gene in humans. Kisspeptins are ligands of the G-protein coupled receptor, GPR54. Kiss1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. Kisspeptin-GPR54 signaling has an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty, the extent of which is an area of ongoing research. Gonadotropin-releasing hormone is released from the hypothalamus to act on the anterior pituitary triggering the release of luteinizing hormone (LH), and follicle stimulating hormone (FSH). These gonadotropic hormones lead to sexual maturation and gametogenesis. Disrupting GPR54 signaling can cause hypogonadotrophic hypogonadism in rodents and humans. The Kiss1 gene is located on chromosome 1. It is transcribed in the brain, adrenal gland, and pancreas.
G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the GPER gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible for some of the rapid effects that estradiol has on cells.
The KiSS1-derived peptide receptor is a G protein-coupled receptor which binds the peptide hormone kisspeptin (metastin). Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues. Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.
The neuropeptide B/W receptors are members of the G-protein coupled receptor superfamily of integral membrane proteins which bind the neuropeptides B and W. These receptors are predominantly expressed in the CNS and have a number of functions including regulation of the secretion of cortisol.
Estrogen-related receptor alpha (ERRα), also known as NR3B1, is a nuclear receptor that in humans is encoded by the ESRRA gene. ERRα was originally cloned by DNA sequence homology to the estrogen receptor alpha, but subsequent ligand binding and reporter-gene transfection experiments demonstrated that estrogens did not regulate ERRα. Currently, ERRα is considered an orphan nuclear receptor.
Neuropeptides B/W receptor 1, also known as NPBW1 and GPR7, is a human protein encoded by the NPBWR1 gene. As implied by its name, it and related gene NPBW2 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 and stria terminalis. When originally discovered in 1995, these receptors had no known ligands 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.
Neuropeptides B/W receptor 2, also known as NPBW2, is a human protein encoded by the NPBWR2 gene.
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.
Pyroglutamylated RFamide peptide receptor also known as orexigenic neuropeptide QRFP receptor or G-protein coupled receptor 103 (GPR103) is a protein that in humans is encoded by the QRFPR gene.
Prokineticin receptor 2 (PKR2), is a dimeric G protein-coupled receptor encoded by the PROKR2 gene in humans.
G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene.
G-protein coupled receptor 3 is a protein that in humans is encoded by the GPR3 gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction.
NPW is a gene that in humans encodes Neuropeptide W protein.
Pulsatile secretion is a biochemical phenomenon observed in a wide variety of cell and tissue types, in which chemical products are secreted in a regular temporal pattern. The most common cellular products observed to be released in this manner are intercellular signaling molecules such as hormones or neurotransmitters. Examples of hormones that are secreted pulsatilely include insulin, thyrotropin, TRH, gonadotropin-releasing hormone (GnRH) and growth hormone (GH). In the nervous system, pulsatility is observed in oscillatory activity from central pattern generators. In the heart, pacemakers are able to work and secrete in a pulsatile manner. A pulsatile secretion pattern is critical to the function of many hormones in order to maintain the delicate homeostatic balance necessary for essential life processes, such as development and reproduction. Variations of the concentration in a certain frequency can be critical to hormone function, as evidenced by the case of GnRH agonists, which cause functional inhibition of the receptor for GnRH due to profound downregulation in response to constant (tonic) stimulation. Pulsatility may function to sensitize target tissues to the hormone of interest and upregulate receptors, leading to improved responses. This heightened response may have served to improve the animal's fitness in its environment and promote its evolutionary retention.
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