QRFP-Deficient Mice Are Hypophagic, Lean, Hypoactive and Exhibit Increased Anxiety-Like Behavior

Okamoto, K.; Yamasaki, Miwako; Takao, Keizo; Soya, Shingo; Iwasaki, Masanori; S, Koh; Magoori, Kenta; Sakakibara, Iori; Miyakawa, Tsuyoshi; Mieda, Michihiro; Watanabe, Masahiko; Sakai, Juro; Yanagisawa, Masashi; Sakurai, Takeshi

doi:10.1371/journal.pone.0164716

Cited by 32 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phenotype of QRFP‐deficient mice (Okamoto et al, ) has confirmed pharmacological data showing that 26RFa/QRFP displays orexigenic and anxiogenic properties (Chartrel et al, ; Do Rego et al, ; Moriya et al, ; Takayasu et al, ; Primeaux et al, ) and stimulates locomotor activity (Do Rego et al, ; Takayasu et al, ). Search for association between SNPs within the human QRFP gene with eating and mood disorders will be required to determine whether 26RFa/QRFP exerts similar activities in humans.…”

Section: Discussionmentioning

confidence: 74%

“…Notably, chronic administration of QRFP produced a transient increase in food intake, weight gain and adiposity in mice consuming a standard chow diet and increased body weight and adiposity in mice fed a moderately fat diet (Moriya et al, 2006). The recent observation that QRFP-deficient mice are hypophagic and lean (Okamoto et al, 2016) strongly supports the notion that 26RFa/QRFP is a potent orexigenic peptide.…”

Section: Biological and Pharmacological Effects Of Qfrp Peptidesmentioning

confidence: 79%

“…Intracerebroventricular injection of 26RFa in mice reduces anxious behaviour in elevated plus maze test, and this effect is mediated via GABAergic and β-adrenergic transmission (Palotai and Telegdy, 2016). Consistent with an anxiolytic effect of 26RFa, QRFP-deficient mice exhibit exacerbated anxiety-like behaviour (Okamoto et al, 2016). Conversely, i.c.v.…”

Section: Biological and Pharmacological Effects Of Qfrp Peptidesmentioning

confidence: 82%

“…injection of 26RFa and QRFP dosedependently increases locomotor activity in mice (Do Rego et al, 2006;Takayasu et al, 2006). The observation that qrfp À/À mice are hypoactive (Okamoto et al, 2016) supports a physiological role of the 26RFa/QRFP-QRFP receptor system in the control of locomotor activity. Interestingly, the effect of 26RFa on locomotion is mimicked by the Nterminal peptide 26RFa (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) , whereas the central segment 26RFa (8)(9)(10)(11)(12)(13)(14)(15)(16) and the C-terminal segment 26RFa (20)(21)(22)(23)(24)(25)(26) are devoid of effect on horizontal and vertical locomotor activities.…”

Section: Biological and Pharmacological Effects Of Qfrp Peptidesmentioning

confidence: 96%

“…26RFa/QRFP knockout QRFP (farp-5) gene deficient mice (QRFP À/À ) have been generated by homologous recombination in ES cells of the 129SvJ strain and implanted in C57 blastocyts (Okamoto et al, 2016). QRFP À/À mice are hypophagic and lean and display increased anxiety-like behaviour, decreased wakefulness time during the dark period and reduced locomotor activity (Okamoto et al, 2016; see 'Effects of QRFP peptides on the CNS' section).…”

Section: Distribution Of 26rfa/qrfp In Peripheral Organsmentioning

confidence: 99%

See 4 more Smart Citations

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

Leprince

Bagnol

Bureau

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

This article, contributed by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee for the QRFP receptor, confirms the existing nomenclature for this receptor, and reviews our current understanding of its structure, pharmacology and functions, and likely physiological roles in health and disease. More information on this receptor can be found in the Concise Guide to PHARMACOLOGY The RFamide neuropeptide 26RFa was first isolated from the brain of the European green frog on the basis of cross-reactivity with antibodies raised against bovine neuropeptide FF (NPFF). 26RFa and its N-terminally extended form glutamine RF-amide peptide (QRFP) have been identified as cognate ligands of the former orphan receptor GPR103, now renamed glutamine RF-amide peptide receptor (QRFP receptor). The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including humans, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei. The 26RFa/QRFP transcript is also present in various organs especially in endocrine glands. While humans express only one QRFP receptor, two isoforms are present in rodents. The QRFP receptor genes are widely expressed in the CNS and in peripheral tissues, notably in bone, heart, kidney, pancreas and testis. Structure-activity relationship studies have led to the identification of low MW peptidergic agonists and antagonists of QRFP receptor. Concurrently, several selective non-peptidic antagonists have been designed from high-throughput screening hit optimization. Consistent with the widespread distribution of QRFP receptor mRNA and 26RFa binding sites, 26RFa/QRFP exerts a large range of biological activities, notably in the control of energy homeostasis, bone formation and nociception that are mediated by QRFP receptor or NPFF2. The present report reviews the current knowledge concerning the 26RFa/QRFP-QRFP receptor system and discusses the potential use of selective QRFP receptor ligands for therapeutic applications.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Biological and Pharmacological Effects Of Qfrp Peptidesmentioning

confidence: 79%

Section: Biological and Pharmacological Effects Of Qfrp Peptidesmentioning

confidence: 82%

Section: Biological and Pharmacological Effects Of Qfrp Peptidesmentioning

confidence: 96%

Section: Distribution Of 26rfa/qrfp In Peripheral Organsmentioning

confidence: 99%

See 3 more Smart Citations

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

Leprince

Bagnol

Bureau

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

show abstract

The variations in human orphan G protein‐coupled receptor QRFPR affect PI3K‐AKT‐mTOR signaling

Lou

et al. 2021

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background QRFPR is a recently identified member of the G protein‐coupled receptor and is an orphan receptor for 26Rfa, which plays important role in the regulation of many physiological functions. Methods Here, we employed whole exome sequencing (WES) to examine the patients with intellectual disability (ID) and difficulty in feeding. We performed SIFT and PolyPhen2 predictions for the variants. The structure model was built from scratch by I‐TASSER. Here, results derived from a number of cell‐based functional assays, including shRNA experiment, intracellular Ca2+ measurement, the expression of PI3 K‐AKT‐mTOR, and phosphorylation. The functional effect of QRFPR variants on PI3K‐AKT‐mTOR signaling was evaluated in vitro transfection experiments. Result Here, we identified two QRFPR variants at c.202 T>C (p.Y68H) and c.1111C>T (p.R371W) in 2 unrelated individuals. Structural analysis revealed that p.Y68H and p.R371W variants may affect the side chain structure of adjacent amino acids causing reduced binding of QRFPR to 26Rfa. The results show that QRFPR stimulated by 26Rfa leading to the transient rise of intracellular Ca2+. The QRFPR variations p.Y68H and p.R371 W can reduce the mobilization of intracellular Ca2+. The phosphorylation levels of the PI3K, Akt, and mTOR were significantly up‐ or downregulated by QRFPR overexpression or silencing, respectively. The QRFPR variations inhibited PI3K‐AKT‐mTOR signaling, resulting in downregulation of p‐mTOR. Conclusions Our findings suggest that QRFPR acts as important role in neurodevelopment, and the effects of QRFPR are likely to be mediated by the Ca2+‐dependent PI3K‐AKT‐mTOR pathways. Importantly, these findings provide a foundation for future elucidation of GPCR‐mediated signaling and the physiological implications.

show abstract

Pyroglutamylated RFamide Peptide

Ukena¹,

Tsutsui²

2016

Handbook of Hormones

View full text Add to dashboard Cite

QRFP-Deficient Mice Are Hypophagic, Lean, Hypoactive and Exhibit Increased Anxiety-Like Behavior

Cited by 32 publications

References 39 publications

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

The variations in human orphan G protein‐coupled receptor QRFPR affect PI3K‐AKT‐mTOR signaling

Pyroglutamylated RFamide Peptide

Contact Info

Product

Resources

About