Neuropeptide W-23 (human)

Neuropeptide W-23(human), the active form of Neuropeptide W, is an endogenous ligand for NPBW1 and NPBW2. Sequence: Trp-Tyr-Lys-His-Val-Ala-Ser-Pro-Arg-Tyr-His-Thr-Val-Gly-Arg-Ala-Ala-Gly-Leu-Met-Gly-Leu.

In Vitro:NPW-23 increases the ICa,L in transfected human embryonic kidney 293 cells and VSMCs via GPR7. NPW-23 increases the expression of pan phospho-PKC, intracellular diacylglycerol level, and the second messenger catalyzed by PLC[1].

In Vivo:NPW-23 increases pressure-induced vasotone of the rat mesenteric arteries. Importantly, the expression of NPW is decreased in the hypertensive rats[1]. NPW-23 (0.3 nmol, 1.0 nmol, and 3.0 nmol) induces significant increases in mean arterial pressure (MAP) in conscious, freely moving male rats. Rats that receive either 1.0 or 3.0 nmol NPW-23 demonstrate a significant increase in total activity, ambulatory activity, and duration of stereotypy. NPW-23 fails to elevate MAP in rats pretreated with phentolamine. NPW-23-induced increases in total activity, ambulatory activity, and duration of stereotypy are reduced significantly by pretreatment with the orexin type 1 receptor (OX1R) antagonist, SB-408124[2].

References:
[1]. Ji L, et al. Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7. J Hypertens. 2015 Dec;33(12):2431-42. [2]. Pate AT, et al. Neuropeptide W increases mean arterial pressure as a result of behavioral arousal. Am J Physiol Regul Integr Comp Physiol. 2013 Oct 1;305(7):R804-10.

The NPB/NPW neuropeptide system and its role in regulating energy homeostasis, pain, and emotion.[Pubmed:18204824]

Results Probl Cell Differ. 2008;46:239-56.

Neuropeptide B (NPB) and neuropeptide W (NPW) are neuropeptides that were recently identified as endogenous ligands for the previously orphan G-protein coupled receptors, GPR7 (NPBWR1) and GPR8 (NPBWR2). This neuropeptide system is thought to have a role in regulating feeding behavior, energy homeostasis, neuroendocrine function, and modulating inflammatory pain. Strong and discrete expression of their receptors in the extended amygdala suggests a potential role in regulating stress responses, emotion, anxiety and fear; however, there have been no functional studies to date to support this possibility. Future studies of NPB/NPW using both pharmacological and phenotypic analysis of genetically engineered mice will lead to further elucidation of the physiological role of this novel neuropeptide system.

Injection of neuropeptide W into paraventricular nucleus of hypothalamus increases food intake.[Pubmed:15886360]

Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1727-32.

Neuropeptide W (NPW) is an endogenous ligand for G protein-coupled receptor 7 (GPR7). There are two forms of the peptide, designated as neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). In the current study we found that intracerebroventricular administration of NPW23 increased c-Fos immunoreactivity (IR) in a variety of brain sites, many of which are involved in the regulation of feeding. In particular, we noted that c-Fos IR levels were increased in hypocretin-expressing neurons in the perifornical region of the lateral hypothalamus (LH). We then studied whether injection of NPW23 into the paraventricular nucleus of the hypothalamus (PVN) and the LH increased food intake over a 24-h time period. Intra-PVN injection of NPW23 at doses ranging from 0.1 to 3 nmol increased feeding for up to 4 h, and doses ranging from 0.3 to 3 nmol increased feeding for up to 24 h. In contrast, only the 3-nmol dose of NPW23 increased feeding after administration into the LH. Together, these data suggest a modulatory role for NPW in the control of food intake.

Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8.[Pubmed:12401809]

J Biol Chem. 2003 Jan 10;278(2):776-83.

GPR7 and GPR8 are two structurally related orphan G protein-coupled receptors, presenting high similarities with opioid and somatostatin receptors. Two peptides, L8 and L8C, derived from a larger precursor, were recently described as natural ligands for GPR8 (Mori, M., Shimomura, Y., Harada, M., Kurihara, M., Kitada, C., Asami, T., Matsumoto, Y., Adachi, Y., Watanabe, T., Sugo, T., and Abe, M. (December, 27, 2001) World Patent Cooperation Treaty, Patent Application WO 01/98494A1). L8 is a 23-amino acid peptide, whereas L8C is the same peptide with a C terminus extension of 7 amino acids, running through a dibasic motif of proteolytic processing. Using as a query the amino acid sequence of the L8 peptide, we have identified in DNA databases a human gene predicted to encode related peptides and its mouse ortholog. By analogy with L8 and L8C, two peptides, named L7 and L7C could result from the processing of a 125-amino acid human precursor through the alternative usage of a dibasic amino acid motif. The activity of these four peptides was investigated on GPR7 and GPR8. In binding assays, L7, L7C, L8, and L8C were found to bind with low nanomolar affinities to the GPR7 and GPR8 receptors expressed in Chinese hamster ovary (CHO)-K1 cells. They inhibited forskolin-stimulated cAMP accumulation through a pertussis toxin-sensitive mechanism. The tissue distribution of prepro-L7 (ppL7) and prepro-L8 (ppL8) was investigated by reverse transcription-PCR. Abundant ppL7 transcripts were found throughout the brain as well as in spinal cord, spleen, testis, and placenta; ppL8 transcripts displayed a more restricted distribution in brain, with high levels in substantia nigra, but were more abundant in peripheral tissues. The ppL7 and ppL8 genes therefore encode the precursors of a class of peptide ligands, active on two receptor subtypes, GPR7 and GPR8. The distinct tissue distribution of the receptor and peptide precursors suggest that each ligand and receptor has partially overlapping but also specific roles in this signaling system.

Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8.[Pubmed:12130646]

J Biol Chem. 2002 Sep 27;277(39):35826-32.

The structurally related orphan G-protein-coupled receptors GPR7 and GPR8 are expressed in the central nervous system, and their ligands have not been identified. Here, we report the identification of the endogenous ligand for both of these receptors. We purified the peptide ligand from porcine hypothalamus using stable Chinese hamster ovary cell lines expressing human GPR8 and cloned the cDNA encoding its precursor protein. The cDNA encodes two forms of the peptide ligand with lengths of 23 and 30 amino acid residues as mature peptides. We designated the two ligands neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). The amino acid sequence of NPW23 is completely identical to that of the N-terminal 23 residues of NPW30. Synthetic NPW23 and NPW30 activated and bound to both GPR7 and GPR8 at similar effective doses. Intracerebroventricular administration of NPW23 in rats increased food intake and stimulated prolactin release. These findings indicate that neuropeptide W is the endogenous ligand for both GPR7 and GPR8 and acts as a mediator of the central control of feeding and the neuroendocrine system.