Identification of a Neuropeptide Modified with Bromine as an Endogenous Ligand for GPR7

Fujii, Ryo; Yoshida, Hiromi; Fukusumi, Shoji; Habata, Yugo; Hashimoto, Masaki; Kawamata, Yuji; Yano, Takahiko; Hinuma, Shuji; Kitada, Chieko; Asami, Taichi; Mori, Masataka; Fujisawa, Yukio; Fujino, Masahiko

doi:10.1074/jbc.m205883200

Cited by 150 publications

(145 citation statements)

References 19 publications

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…NPW, on the other hand, has been identified in two molecular forms of 23 and 30 amino acids (NPW23 and NPW30) respectively. The amino acid sequence of NPW23 is identical to the first 23 Nterminal amino acids of NPW30 (4,5). Expression of NPB, NPW and their receptor gene was found to be present in the central nervous system and in the peripheral organs of humans, rats, and mice (1,2,(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 86%

Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat

Ruciński

Nowak²,

Chmielewska³

et al. 2007

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Neuropeptide B/W receptor 1 (NPBWR1) and neuropeptide B/W receptor 2 (NPBWR2) are two structurally related orphan receptors linked to protein G. In rodents NPBWR2 is absent, and its counterpart is described as being similar to neuropeptide B/W receptor 2. Endogenous ligands of these receptors have been identified. One of them is 29 amino acid residues long, uniquely modified with bromine and, thus, termed neuropeptide B (NPB). The other, neuropeptide W (NPW), has been identified in two molecular forms of 23 and 30 amino acids (NPW23 and NPW30), respectively. Both NPB and NPW affect food intake and energy expenditure. Since leptin, a potent anti-obesity hormone, and insulin are involved in the control of energy homeostasis, the present study aimed to investigate whether NPB and NPW affect leptin and insulin secretion in the rat. RT-PCR technique revealed the presence of ppNPB, ppNPW, NPBWR1 and NPBWR2-like mRNAs in isolated pancreatic islets of the rat. NPB and NPW immunoreactivities were observed in all of the cells of the pancreatic islets. Only when a higher dose was administered (3 nmol/100 g body weight) did NPW transiently lower blood insulin levels whereas NPB injection did not alter insulinaemia in the studied rats. At 30 min, but not 60, of the experiment, NPW notably lowered blood leptin concentrations at both tested doses. On the contrary, NPB injections had no effect on blood leptin and insulin concentrations. Thus, the results suggest that NPW but not NPB exerts a potent suppressive effect on blood leptin concentrations in the rat, and this mechanism may be involved in NPW regulation of energy homeostasis.

show abstract

Section: Introductionmentioning

confidence: 86%

Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat

Ruciński

Nowak²,

Chmielewska³

et al. 2007

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…To summarize, NPB and GPR7 mRNAs were identified in the pituitary, testis and ovary, but only GPR7 mRNA was detected in the thyroid, pancreas and adrenals (1). NPW-immunoreactivity (IR) was found in the larger diameter cells of the anterior pituitary (13).…”

Section: Introductionmentioning

confidence: 99%

“…In rodents GPR8 is absent, its counterpart being described as GPR8-like receptor (GPR8-LR) (3). NPB, NPW and their receptors are highly expressed in the human and rodent central nervous system (especially hypothalamus) (1)(2)(3)(4)(5)(6)(7)(8), and findings have been accumulated that these peptides are involved in the central regulation of feeding behavior and energy homeostasis (6,(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of neuropeptides B and W and their receptors in endocrine glands of the rat

Hochol¹,

Belloni²,

Ruciński³

et al. 2006

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Neuropeptides B and W (NPB and NPW) have been identified as endogenous ligands of the G protein-coupled receptors (GPR) 7 and 8, which in humans are expressed in the hypothalamus and probably involved in the regulation of energy homeostasis and feeding behavior. GPR8 is absent in the rat, where the GPR8-like receptor (GPR8-LR) has been described. Reverse transcription-polymerase chain reaction detected the expression of NPB, NPW, GPR7 and GPR8-LR mRNAs in the hypothalamus, anterior pituitary, thyroid and parathyroid glands, pancreatic islets, adrenal glands, ovary and testis of the rat. Immunocytochemistry demonstrated the presence of NPB and NPW immunoreactivities in these same glands. Radioimmune assay showed that the bolus intraperitoneal injection of 2 nmol/100 g NPB or NPW raised the plasma levels of parathyroid hormone, corticosterone and testosterone. NPB also increased the blood concentration of thyroxine, and NPW that of ACTH and estradiol. Taken together, these findings allow us to suggest that NPB and NPW play a role in the autocrine-paracrine functional regulation of the endocrine system in the rat.

show abstract

“…Whereas humans and other mammals also express GPR8, a highly related G protein-coupled receptor, GPR8 is absent in rats and mice (8). Recently, several groups have identified endogenous peptide ligands NPB and NPW (alternatively called L7 and L8) for GPR7 and GPR8 by using reverse pharmacology (9)(10)(11)(12). NPB and NPW are expressed from two different genes and together with GPR7 constitute a neuropeptide receptor pathway.…”

mentioning

confidence: 99%

Targeted disruption of GPR7, the endogenous receptor for neuropeptides B and W, leads to metabolic defects and adult-onset obesity

Ishii

Friedman

2003

Proc. Natl. Acad. Sci. U.S.A.

107

View full text Add to dashboard Cite

Gold-thioglucose (GTG) induces lesions in the ventromedial nucleus of the hypothalamus, resulting in hyperphagia and obesity. To identify genes involved in the hypothalamic regulation of energy homeostasis, we used a screen for genes that are dysregulated in GTG-induced obese mice. We found that GPR7, the endogenous G protein-coupled receptor for the recently identified ligands neuropeptide B and neuropeptide W, was down-regulated in hypothalamus after GTG treatment. Here we show that male GPR7؊͞؊ mice develop an adult-onset obese phenotype that progressively worsens with age and was greatly exacerbated when animals are fed a high-fat diet. GPR7؊͞؊ male mice were hyperphagic and had decreased energy expenditure and locomotor activity. Plasma levels of glucose, leptin, and insulin were also elevated in these mice. GPR7؊͞؊ male mice had decreased hypothalamic neuropeptide Y RNA levels and increased proopiomelanocortin RNA levels, a set of effects opposite to those evident in ob͞ob mice. Furthermore, ob͞ob GPR7؊͞؊ and Ay͞a GPR7؊͞؊ double mutant male mice had an increased body weight compared with normal ob͞ob or Ay͞a male mice, suggesting that the obesity of GPR7؊͞؊ mice is independent of leptin and melanocortin signaling. Female mice did not show any significant weight increase or associated metabolic defects. These data suggest a potential role for GPR7 and its endogenous ligands, neuropeptide B and neuropeptide W, in regulating energy homeostasis independent of leptin and melanocortin signaling in a sexually dimorphic manner.M aintenance of a stable body weight in mammals requires the precise balance of energy input (feeding) and energy output (energy expenditure). The hypothalamus has been identified as a main central regulator controlling energy homeostasis through a complex neuronal circuit involving classical neurotransmitters and a number of neuropeptides (1). Classical studies of animals with hypothalamic lesions have suggested that a ''satiety center'' in the ventromedial hypothalamic nucleus (VMH) can induce a state of negative energy balance and that a ''feeding center'' in the lateral hypothalamic area (LH) can induce a state of positive energy balance (1, 2). Thus, VMH lesions lead to hyperphagia and obesity, and LH lesions cause hypophagia and leanness. VMH lesions can be either electrolytic or chemical, as a single i.p. injection of gold-thioglucose (GTG) selectively ablates neurons in the VMH, causing obesity (3, 4). Evidence suggests that GTG selectively targets glucose responsive neurons in the VMH and induces neurotoxicity specifically because of the gold moiety (5, 6).We set out to test the possibility that genes regulating energy homeostasis can be found by identifying cDNAs whose expression levels differed between GTG-treated and saline-treated control animals. Hypothalamic genes that are ablated or downregulated after GTG treatment could possibly account for some part of the hyperphagic obese syndrome in mice with selective VMH lesions. In our study, we identified one such gene, GPR7, the en...

show abstract

Identification of a Neuropeptide Modified with Bromine as an Endogenous Ligand for GPR7

Cited by 150 publications

References 19 publications

Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat

Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat

Expression of neuropeptides B and W and their receptors in endocrine glands of the rat

Targeted disruption of GPR7, the endogenous receptor for neuropeptides B and W, leads to metabolic defects and adult-onset obesity

Contact Info

Product

Resources

About