Neuropeptide W

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]

Neuropeptide W
Neuropeptide W primary sequence using three letters code. N-terminal represented in blue. C-terminal represented in red.
Identifiers
Symbol?
UniProtQ8N729
Other data
WikidataQ21173201

Structure

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.

Location

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]

Function

Neuropeptide W in CNS

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 to anterior hypophysis. This stimulates both the need of water (thirst) and need of 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]

Neuropepdide W in peripheral tissues

Nevertheless, function and physiological role of peripheric neuropeptid W is not clearly known.

References
  1. Takenoya F, Kageyama H, Hirako S, Ota E, Wada N, Ryushi T, Shioda S (December 2012). "Neuropeptide W". Frontiers in Endocrinology. 3: 171. doi:10.3389/fendo.2012.00171. PMC 3527818. PMID 23267349.
  2. "Neuropeptide W/neuropeptide B receptors | G protein-coupled receptors | IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org. Retrieved 2020-11-08.
  3. Zhang Y, Wang Z, Parks GS, Civelli O (2011). "Novel neuropeptides as ligands of orphan G protein-coupled receptors". Current Pharmaceutical Design. 17 (25): 2626–31. doi:10.2174/138161211797416110. PMC 5828022. PMID 21728976.
  4. Chen, C; Huang, H; Wu, CH (July 23, 2020). "UniProtKB - Q8N729 (NPW_HUMAN)". Protein Bioinformatics Databases and Resources. Retrieved 26 October 2020.
  5. "Neuropeptide W/neuropeptide B receptors | G protein-coupled receptors | IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org. Retrieved 2020-11-08.
  6. Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, et al. (September 2002). "Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8". The Journal of Biological Chemistry. 277 (39): 35826–32. doi:10.1074/jbc.M205337200. PMID 12130646.
  7. Takenoya F, Kageyama H, Shiba K, Date Y, Nakazato M, Shioda S (July 2010). "Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism?". Annals of the New York Academy of Sciences. 1200: 162–9. doi:10.1111/j.1749-6632.2010.05642.x. PMID 20633144.
  8. Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, et al. (January 2003). "Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8". The Journal of Biological Chemistry. 278 (2): 776–83. doi:10.1074/jbc.M206396200. PMID 12401809.
  9. Dvorakova MC (2018-07-24). "Distribution and Function of Neuropeptides W/B Signaling System". Frontiers in Physiology. 9: 981. doi:10.3389/fphys.2018.00981. PMC 6067035. PMID 30087623.
  10. Taylor MM, Yuill EA, Baker JR, Ferri CC, Ferguson AV, Samson WK (January 2005). "Actions of neuropeptide W in paraventricular hypothalamus: implications for the control of stress hormone secretion". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 288 (1): R270-5. doi:10.1152/ajpregu.00396.2004. PMID 15345475.
  11. Baker JR, Cardinal K, Bober C, Taylor MM, Samson WK (July 2003). "Neuropeptide W acts in brain to control prolactin, corticosterone, and growth hormone release". Endocrinology. 144 (7): 2816–21. doi:10.1210/en.2002-0161. PMID 12810535.
  12. Mondal MS, Yamaguchi H, Date Y, Shimbara T, Toshinai K, Shimomura Y, et al. (November 2003). "A role for neuropeptide W in the regulation of feeding behavior". Endocrinology. 144 (11): 4729–33. doi:10.1210/en.2003-0536. PMID 12959997.
  13. Mazzocchi G, Rebuffat P, Ziolkowska A, Rossi GP, Malendowicz LK, Nussdorfer GG (June 2005). "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". The Journal of Clinical Endocrinology and Metabolism. 90 (6): 3466–71. doi:10.1210/jc.2004-2132. PMID 15797961.
  14. Singh G, Davenport AP (August 2006). "Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system". British Journal of Pharmacology. 148 (8): 1033–41. doi:10.1038/sj.bjp.0706825. PMC 1752024. PMID 16847439.
  15. Pate AT, Yosten GL, Samson WK (October 2013). "Neuropeptide W increases mean arterial pressure as a result of behavioral arousal". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 305 (7): R804-10. doi:10.1152/ajpregu.00119.2013. PMC 3798801. PMID 23926134.
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