Neuropeptide W-30

Discovery
NPW human gene has been identified by Tanaka et al., (2003), who also cloned the mouse Neuropeptide W gene and reported restricted expression in specific neurons in the midbrain and brainstem. Shimomura et al., (2002) identified Neuropeptide W-23 and NPW-30. Brezillon et al., (2003) reported that NPW is expressed in substantia nigra, lymphoblastic leukemia, fetal kidney, colorectal adenocarcinoma, and trachea. Kitamura et al., (2006) and Jackson et al., (2006) localized expression of NPW in various areas of the rat Brain. Takenoya et al., (2008) reported that neuropeptide W is found in neurons also expressing orexin and melanin concentrating hormone. Hochol et al.,(2006) reported the expression of NPW and its receptors in hypothalamus, anterior pituitary, thyroid and parathyroid glands, pancreatic islets, adrenal glands, ovary and testis of the rat 1-8.

Structural Characteristics
NPW is a neuropeptide hormone of 30 amino acids derived from a prepro-protein of 165 amino acids (termed PPNPW) 3.

Mode of Action
The receptors for neuropeptide W have been identified in humans as the G-protein-coupled receptors GRP7 [G-protein-coupled receptor-7] and GPR8 [G-protein-coupled receptor-8] . The short form of neuropeptide W is the most potent receptor agonist 1-3. GPR8 receptors are absent in rodents, where the GPR8-LR [GPR8-like receptor] has been described9. Receptors have been shown to be expressed in neurons in various brain areas10, adrenocortical cells. Rat adrenocortical cells produce Neuropeptide W and also express the receptor, suggesting autocrine and/or paracrine acivities 7.

Functions
Hochol et al., (2006) have suggested a role of NPW in the autocrine and/or paracrine functional regulation of the endocrine system in the rat. Intraperitoneal of NPW raises plasma levels of parathyroid hormone, corticosterone and testosterone, ACTH and estradiol. NPW enhances ACTH stimulated aldosterone secretion from adrenocortical cells and does not affect either basal or ACTH stimulated corticosterone production. Prolonged exposure to NPW raises corticosterone secretion and increases the proliferation rate of cultured cells 7, 8. Endogenous NPW may play a physiologically relevant role in the neuroendocrine response to stress that may modulate the hypothalamic-pituitary-adrenocortical axis. NPW has been reported to elevate prolactin and corticosterone and lowering growth hormone levels in the circulation. However, as shown by in vitro stimulation of dispersed anterior pituitary cells, it does not itself act as a true releasing or inhibiting factor in the anterior pituitary gland. The central effects of NPW to inhibit growth hormone release result from activation of arcuate somatostatin neurons, which could result in an inhibition of neurons expressing growth hormone releasing hormone. Centrally administered NP W-30 activates magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei and significantly increases plasma arginine-vasopressin and plasma oxytocin levels.
NPW acts as an endogenous catabolic signaling molecule in the brain. Injection of NPW into paraventricular nucleus of hypothalamus increases food intake. Both forms of neuropeptide W suppress dark phase and fasting-induced food intake, and also increase body temperature and heat production. Continuous intracerebroventricular infusion of NPW suppresses feeding and body weight gain, whereas administration of anti-NPW IgG stimulates feeding. NPW is a potent suppressor of blood leptin levels in the rat. It potentiates glucose-induced insulin release and calcium influx in pancreatic beta-cells
Yamamoto et al., (2005) have reported an anti-hyperalgesic effect of intrathecally administered NPW23 in tests of inflammatory pain in rats. Yu et al (2007) have reported cardiovascular activities of NPW30. Intracerebroventricular administration increases the mean arterial pressure, heart rate, and plasma norepinephrine and epinephrine levels. Intravenously administered NPW30 has no significant effects on mean arterial pressure, heart rate 11-22.

References
1. Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori M, Onda H, Fujino M.(2002). Identification of Neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8. J Biol Chem., 277(39):35826-35832.
2. Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M.(2003). Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8. J Biol Chem., 278:776-783.
3. Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N, Garry MG, Lerner MR, King DS, O'Dowd BF, Sakurai T, Yanagisawa M.(2003). Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. PNAS., 100(10):6251-6256.
4. Kitamura Y, Tanaka H, Motoike T, Ishii M, Williams SC, Yanagisawa M, Sakurai T.(2006). Distribution of Neuropeptide W immunoreactivity and mRNA in adult rat brain. Brain Res., 1093(1):123-134.
5. Jackson VR, Lin SH, Wang Z, Nothacker HP, Civelli O. (2006). A study of the rat neuropeptide B/Neuropeptide W system using in situ techniques. J Comp Neurol., 497(3):367-383.
6. Takenoya F, Kitamura S, Kageyama H, Nonaka N, Seki M, Itabashi K, Date Y, Nakazato M, Shioda S (2008). Neuronal interactions between Neuropeptide W- and orexin- or melanin-concentrating hormone-containing neurons in the rat hypothalamus. Regul Pep., 145(1-3):159-164.
7. Hochol A, Albertin G, Nussdorfer GG, Spinazzi R, Ziolkowska A, Rucinski M, Malendowicz LK.(2004). Effects of neuropeptides B and W on the secretion and growth of rat adrenocortical cells. Intl J Mol Med.,14(5): 843-847 (2004);
8. Hochol A, Belloni AS, Rucinski M, Ziolkowska A, Di Liddo R, Nussdorfer GG, Malendowicz LK. (2006). Expression of neuropeptides B and W and their receptors in endocrine glands of the rat. Int J Mol Med., 18(6):1101-1106.
9. Lee DK, Nguyen T, Porter CA, Cheng R, George SR, O'Dowd BF. (1999). Two related G protein-coupled receptors: the distribution of GPR7 in rat brain and the absence of GPR8 in rodents. Brain Res Mol Brain Res., 71(1):96-103.
10. Singh G, Maguire JJ, Kuc RE, Fidock M, Davenport AP.(2004). Identification and cellular localisation of NPW1 (GPR7) receptors for the novel Neuropeptide W-23 by [125I]-NPW radioligand binding and immunocytochemistry. Brain Res., 1017(1-2):222-226.
11. Taylor MM, Yuill EA, Baker JR, Ferri CC, Ferguson AV, Samson WK. (2005). Actions of Neuropeptide W in paraventricular hypothalamus: implications for the control of stress hormone secretion. Am J Physiol Regul Integr Comp Physiol 288(1): 270-275.
12. Niimi M and Murao K. 2005. Neuropeptide W as a stress mediator in the hypothalamus. Endocrine., 27(1): 51-54.
13. Baker JR, Cardinal K, Bober C, Taylor MM, Samson WK. (2003). Neuropeptide W acts in brain to control prolactin, corticosterone, and growth hormone release. Endocrinology., 144(7):2816-2821.
14. Price CJ, Samson WK, Ferguson AV. (2008). Neuropeptide W influences the excitability of neurons in the rat hypothalamic arcuate nucleus. Neuroendocrinology., 88(2):88-94.
15. Kawasaki M, Onaka T, Nakazato M, Saito J, Mera T, Hashimoto H, Fujihara H, Okimoto N, Ohnishi H, Nakamura T, Ueta Y. (2006). Centrally administered Neuropeptide W-30 activates magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei with neurosecretion in rats. J Endocrinol., 190(2):213-223.
16. Dezaki K, Kageyama H, Seki M, Shioda S, Yada T.(2008). Neuropeptide W in the rat pancreas: potentiation of glucose-induced insulin release and Ca2+ influx through L-type Ca2+ channels in beta-cells and localization in islets. Regul Pep., 145(1-3):153-158.
17. Levine AS, Winsky-Sommerer R, Huitron-Resendiz S, Grace MK, de Lecea L.(2005). Injection of Neuropeptide W into paraventricular nucleus of hypothalamus increases food intake. Am J Physiol Regul Integr Comp Physiol., 288(6):1727-1732.
18. Mazzocchi G, Rebuffat P, Ziolkowska A, Rossi GP, Malendowicz LK, Nussdorfer GG.(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. J Clin Endocrinol Metab., 90(6):3466-3471.
19. Mondal MS, Yamaguchi H, Date Y, Shimbara T, Toshinai K, Shimomura Y, Mori M, Nakazato M.(2003). A role for Neuropeptide W in the regulation of feeding behavior. Endocrinology., 144(11):4729-4733.
20. Rucinski M, Nowak KW, Chmielewska J, Ziolkowska A, Malendowicz LK.( 2007). Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat. Int J Mol Med., 19(3):401-405.
21. Yamamoto T, Saito O, Shono K, Tanabe S.(2005). Anti-hyperalgesic effects of intrathecally administered Neuropeptide W-23, and neuropeptide B, in tests of inflammatory pain in rats. Brain Res., 1045(1-2):97-106.
22. Yu N, Chu C, Kunitake T, Kato K, Nakazato M, Kannan H.(2007). Cardiovascular actions of central Neuropeptide W in conscious rats. Regul Pep., 138(2-3):82-86.