{{Short description|Mammalian protein found in Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{infobox protein | image=Neuropeptide W primary sequence.png | caption=Neuropeptide W primary sequence using three letters code. N-terminal represented in blue. C-terminal represented in red. | Wikidata =Q21173201 | UniProt =Q8N729 }} '''Neuropeptide W''' or '''preprotein L8''' is a short human neuropeptide.<ref name="Takenoya_2012">{{cite journal | vauthors = Takenoya F, Kageyama H, Hirako S, Ota E, Wada N, Ryushi T, Shioda S | title = Neuropeptide W | journal = Frontiers in Endocrinology | volume = 3 | pages = 171 | date = December 2012 | pmid = 23267349 | pmc = 3527818 | doi = 10.3389/fendo.2012.00171 | doi-access = free }}</ref> 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.<ref>{{Cite web | title = Neuropeptide W/neuropeptide B receptors {{!}} G protein-coupled receptors {{!}} IUPHAR/BPS Guide to PHARMACOLOGY|url=https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=45|access-date=2020-11-08|website=www.guidetopharmacology.org}}</ref><ref>{{cite journal | vauthors = Zhang Y, Wang Z, Parks GS, Civelli O | title = Novel neuropeptides as ligands of orphan G protein-coupled receptors | journal = Current Pharmaceutical Design | volume = 17 | issue = 25 | pages = 2626–2631 | date = 2011 | pmid = 21728976 | pmc = 5828022 | doi = 10.2174/138161211797416110 }}</ref>
== Structure == There are two forms of neuropeptide W whose precursor is encoded by NPW gene.<ref>{{Cite web | vauthors = Chen C, Huang H, Wu C | title = UniProtKB - Q8N729 (NPW_HUMAN) | date = July 23, 2020 | url = https://www.uniprot.org/uniprot/Q8N729 | access-date = 26 October 2020 | website = Protein Bioinformatics Databases and Resources }}</ref>
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.<ref>{{Cite web | title = Neuropeptide W/neuropeptide B receptors {{!}} G protein-coupled receptors {{!}} IUPHAR/BPS Guide to PHARMACOLOGY|url=https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=45|access-date=2020-11-08|website=www.guidetopharmacology.org}}</ref>
The name of neuropeptide W is due to the tryptophan residues located on both sides, the N- side and -C side, in its two mature forms.
== Location== Neuropeptide W was first identified in porcine hypothalamus in 2002.<ref>{{cite journal | vauthors = Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori M, Onda H, Fujino M | title = Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 39 | pages = 35826–35832 | date = September 2002 | pmid = 12130646 | doi = 10.1074/jbc.M205337200 | doi-access = free }}</ref> 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. <ref>{{cite journal | vauthors = Takenoya F, Kageyama H, Shiba K, Date Y, Nakazato M, Shioda S | title = Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism? | journal = Annals of the New York Academy of Sciences | volume = 1200 | issue = 1 | pages = 162–169 | date = July 2010 | pmid = 20633144 | doi = 10.1111/j.1749-6632.2010.05642.x | bibcode = 2010NYASA1200..162T | s2cid = 205934962 }}</ref> 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.<ref>{{cite journal | vauthors = Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M | title = Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 2 | pages = 776–783 | date = January 2003 | pmid = 12401809 | doi = 10.1074/jbc.M206396200 | doi-access = free }}</ref> For the moment, Neuropeptide W location differences between studied species (rat, mouse, chicken, pig) are slight, even though quantities differ between the organs.<ref name="Dvorakova_2018">{{cite journal | vauthors = Dvorakova MC | title = Distribution and Function of Neuropeptides W/B Signaling System | journal = Frontiers in Physiology | volume = 9 | article-number = 981 | date = 2018-07-24 | pmid = 30087623 | pmc = 6067035 | doi = 10.3389/fphys.2018.00981 | doi-access = free }}</ref>
== Function ==
=== Neuropeptide W in CNS === Neuropeptide W in the central nervous system is implicated in feeding activity and energy metabolism, in the adrenal axis stress response, and the regulation of neuroendocrine functions like 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.<ref>{{cite journal | vauthors = Taylor MM, Yuill EA, Baker JR, Ferri CC, Ferguson AV, Samson WK | title = Actions of neuropeptide W in paraventricular hypothalamus: implications for the control of stress hormone secretion | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 288 | issue = 1 | pages = R270–R275 | date = January 2005 | pmid = 15345475 | doi = 10.1152/ajpregu.00396.2004 }}</ref><ref>{{cite journal | vauthors = Baker JR, Cardinal K, Bober C, Taylor MM, Samson WK | title = Neuropeptide W acts in brain to control prolactin, corticosterone, and growth hormone release | journal = Endocrinology | volume = 144 | issue = 7 | pages = 2816–2821 | date = July 2003 | pmid = 12810535 | doi = 10.1210/en.2002-0161 | doi-access = free }}</ref> Neuropeptide W has been shown to have analgesic and anticonvulsant effects, suggesting that its receptors may have useful medical applications.<ref name="Green_2011">{{cite journal | vauthors = Green BR, Smith M, White KL, White HS, Bulaj G | title = Analgesic neuropeptide W suppresses seizures in the brain revealed by rational repositioning and peptide engineering | journal = ACS Chemical Neuroscience | volume = 2 | issue = 1 | pages = 51–56 | date = January 2011 | pmid = 22826747 | pmc = 3400287 | doi = 10.1021/cn1000974 }}</ref>
It seems that regulation of feeding behaviour and energy metabolism is the primary function of the neuropeptide W signaling system.<ref name="Parker_2012">{{cite journal | vauthors = Parker JA, Bloom SR | title = Hypothalamic neuropeptides and the regulation of appetite | journal = Neuropharmacology | volume = 63 | issue = 1 | pages = 18–30 | date = July 2012 | pmid = 22369786 | doi = 10.1016/j.neuropharm.2012.02.004 }}</ref><ref name="Li_2018">{{cite journal | vauthors = Li H, Kentish SJ, Wittert GA, Page AJ | title = The role of neuropeptide W in energy homeostasis | journal = Acta Physiologica | location = Oxford, England | volume = 222 | issue = 1 | date = January 2018 | article-number = e12884 | pmid = 28376284 | doi = 10.1111/apha.12884 }}</ref> 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.<ref>{{cite journal | vauthors = Mondal MS, Yamaguchi H, Date Y, Shimbara T, Toshinai K, Shimomura Y, Mori M, Nakazato M | title = A role for neuropeptide W in the regulation of feeding behavior | journal = Endocrinology | volume = 144 | issue = 11 | pages = 4729–4733 | date = November 2003 | pmid = 12959997 | doi = 10.1210/en.2003-0536 | doi-access = free }}</ref>
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.<ref name="Dvorakova_2018" />
An example of neuroendocrine functions is the regulation of the secretion of cortisol due to the activation or deactivation of neuropeptide B/W receptors.<ref>{{cite journal | vauthors = Mazzocchi G, Rebuffat P, Ziolkowska A, Rossi GP, Malendowicz LK, Nussdorfer GG | title = G protein receptors 7 and 8 are expressed in human adrenocortical cells, and their endogenous ligands neuropeptides B and w enhance cortisol secretion by activating adenylate cyclase- and phospholipase C-dependent signaling cascades | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 6 | pages = 3466–3471 | date = June 2005 | pmid = 15797961 | doi = 10.1210/jc.2004-2132 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Singh G, Davenport AP | title = Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system | journal = British Journal of Pharmacology | volume = 148 | issue = 8 | pages = 1033–1041 | date = August 2006 | pmid = 16847439 | pmc = 1752024 | doi = 10.1038/sj.bjp.0706825 }}</ref>
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.<ref>{{cite journal | vauthors = Pate AT, Yosten GL, Samson WK | title = Neuropeptide W increases mean arterial pressure as a result of behavioral arousal | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 305 | issue = 7 | pages = R804–R810 | date = October 2013 | pmid = 23926134 | pmc = 3798801 | doi = 10.1152/ajpregu.00119.2013 }}</ref>
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.<ref name="Takenoya_2012" />
=== Neuropeptide W in peripheral tissues === While the central roles of neuropeptide W are better studied, it is also important in peripheral tissues in functions such as regulation of vascular muscle tone, regulation of gastric tension sensitive vagus nerve signalling, and insulin secretion.<ref name="Chottova_Dvorakova_2018">{{cite journal | vauthors = Chottova Dvorakova M | title = Distribution and Function of Neuropeptides W/B Signaling System | journal = Frontiers in Physiology | volume = 9 | article-number = 981 | date = 2018 | pmid = 30087623 | pmc = 6067035 | doi = 10.3389/fphys.2018.00981 | doi-access = free }}</ref>
== See also == * Neuropeptide B * Neuropeptide FF
== References == {{Reflist}}
Category:Neuropeptides Category:G proteins Category:Genes on human chromosome 17