256 results match your criteria npff receptor


Lack of neuropeptide FF signalling in mice leads to reduced repetitive behavior, altered drinking behavior, and fuel type selection.

FASEB J 2021 11;35(11):e21980

Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.

Although best known for their involvement in modulating nociception, Neuropeptide FF (NPFF) group peptides have been suggested to fulfil a variety of biological functions such as feeding, anxiety behaviors and thermogenesis. However, evidence supporting these functions of NPFF is mostly pharmacological, leaving the physiological relevance unaddressed. Here we examined the physiological impact of lack of NPFF signalling in both genders using a Npff mouse model. Read More

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November 2021

Single molecule real-time sequencing revealing novel insights on the response to estrogen and androgen exposure in freshwater snails.

Aquat Toxicol 2021 Oct 28;239:105953. Epub 2021 Aug 28.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

The molecular mode of action underpinning the response of mollusks exposure to endocrine disrupting chemicals (EDCs) remains unclear due to a lack of available information regarding their genome. Single molecule real-time (SMRT) sequencing makes it possible to reveal molecular mechanisms by direct sequencing of full-length transcripts. In the present study, the transcriptome profile of the freshwater snail Parafossarulus striatulus after exposure to 17β-estradiol (E2) or 17α-methyltestosterone (MT) was evaluated using SMRT sequencing strategy. Read More

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October 2021

Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.

J Med Chem 2021 09 31;64(18):13394-13409. Epub 2021 Aug 31.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, Gansu Province 730000, PR China.

We previously reported that a multifunctional opioid/neuropeptide FF receptor agonist, DN-9, achieved peripherally restricted analgesia with reduced side effects. To develop stable and orally bioavailable analogues of DN-9, eight lactam-bridged cyclic analogues of DN-9 between positions 2 and 5 were designed, synthesized, and biologically evaluated. cAMP assays revealed that these analogues, except , were multifunctional ligands that activated opioid and neuropeptide FF receptors. Read More

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September 2021

Palmitoylation of Prolactin-Releasing Peptide Increased Affinity for and Activation of the GPR10, NPFF-R2 and NPFF-R1 Receptors: In Vitro Study.

Int J Mol Sci 2021 Aug 18;22(16). Epub 2021 Aug 18.

Biochemistry and Molecular Biology, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic.

The anorexigenic neuropeptide prolactin-releasing peptide (PrRP) is involved in the regulation of food intake and energy expenditure. Lipidization of PrRP stabilizes the peptide, facilitates central effect after peripheral administration and increases its affinity for its receptor, GPR10, and for the neuropeptide FF (NPFF) receptor NPFF-R2. The two most potent palmitoylated analogs with anorectic effects in mice, palm-PrRP31 and palm-PrRP31, were studied in vitro to determine their agonist/antagonist properties and mechanism of action on GPR10, NPFF-R2 and other potential off-target receptors related to energy homeostasis. Read More

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Knockout of NPFFR2 Prevents LPS-Induced Depressive-Like Responses in Mice.

Int J Mol Sci 2021 Jul 16;22(14). Epub 2021 Jul 16.

Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 333, Taiwan.

The precise neural mechanisms underlying the pathogenesis of depression are largely unknown, though stress-induced brain inflammation and serotonergic plasticity are thought to be centrally involved. Moreover, we previously demonstrated that neuropeptide FF receptor 2 (NPFFR2) overexpression provokes depressive-like behaviors in mice. Here, we assess whether NPFFR2 is involved in priming of depressive-like behaviors and downregulation of serotonergic 1A receptor (5HT1AR) after lipopolysaccharide (LPS) treatment. Read More

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Transcriptomic Changes in Mouse Bone Marrow-Derived Macrophages Exposed to Neuropeptide FF.

Genes (Basel) 2021 05 9;12(5). Epub 2021 May 9.

School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.

Neuropeptide FF (NPFF) is a neuropeptide that regulates various biological activities. Currently, the regulation of NPFF on the immune system is an emerging field. However, the influence of NPFF on the transcriptome of primary macrophages has not been fully elucidated. Read More

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Identification of an -acylated-Arg-Leu-NH Dipeptide as a Highly Selective Neuropeptide FF1 Receptor Antagonist That Potently Prevents Opioid-Induced Hyperalgesia.

J Med Chem 2021 06 19;64(11):7555-7564. Epub 2021 May 19.

Laboratoire d'Innovation Thérapeutique, UMR 7200 CNRS, Université de Strasbourg, 74 Route du Rhin, 67401 Illkirch, France.

RFamide-related peptide-3 (RFRP-3) and neuropeptide FF (NPFF) target two different receptor subtypes called neuropeptide FF1 (NPFF1R) and neuropeptide FF2 (NPFF2R) that modulate several functions. However, the study of their respective role is severely limited by the absence of selective blockers. We describe here the design of a highly selective NPFF1R antagonist called RF3286, which potently blocks RFRP-3-induced hyperalgesia in mice and luteinizing hormone release in hamsters. Read More

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RF-amide related peptide-3 (RFRP-3): a novel neuroendocrine regulator of energy homeostasis, metabolism, and reproduction.

Mol Biol Rep 2021 Feb 10;48(2):1837-1852. Epub 2021 Feb 10.

Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

A hypothalamic neuropeptide, RF-amide related peptide-3 (RFRP-3), the mammalian ortholog of the avian gonadotropin-inhibitory hormone (GnIH) has inhibitory signals for reproductive axis via G-protein coupled receptor 147 in mammals. Moreover, RFRP-3 has orexigenic action but the mechanism involved in energy homeostasis and glucose metabolism is not yet known. Though, the RFRP-3 modulates orexigenic action in co-operation with other neuropeptides, which regulates metabolic cues in the hypothalamus. Read More

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February 2021

MCRT, a multifunctional ligand of opioid and neuropeptide FF receptors, attenuates neuropathic pain in spared nerve injury model.

Basic Clin Pharmacol Toxicol 2021 Jun 15;128(6):731-740. Epub 2021 Feb 15.

Department of Animal and Biomedical Sciences, School of Life Sciences, Lanzhou University, Lanzhou, China.

Chimeric peptide MCRT (YPFPFRTic-NH ) was a multifunctional ligand of opioid and neuropeptide FF (NPFF) receptors and reported to be potentially antalgic in acute tail-flick test. Here, we developed spared nerve injury (SNI) model to explore its efficacy in chronic neuropathic pain. Analgesic tolerance, opioid-induced hyperalgesia and gastrointestinal transit were measured for safety evaluation. Read More

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Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats.

Biomedicines 2021 Jan 25;9(2). Epub 2021 Jan 25.

Department of Pathophysiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary.

Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Read More

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January 2021

Expression analysis of neuropeptide FF receptors on neuroendocrine-related neurons in the rat brain using highly sensitive in situ hybridization.

Histochem Cell Biol 2021 Apr 4;155(4):465-475. Epub 2021 Jan 4.

Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku, Tokyo, 113-8602, Japan.

RF-amide peptides, a family of peptides characterized by a common carboxy-terminal Arg-Phe-NH motif, play various physiological roles in the brain including the modulation of neuroendocrine signaling. Neuropeptide FF (NPFF) receptors exhibit a high affinity for all RF-amide peptides, which suggests that the neurons expressing these NPFF receptors may have multiple functions in the brain. However, the distribution of the neurons expressing NPFF receptors in the rat brain remains poorly understood. Read More

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Cellular processes involved in RAW 264.7 macrophages exposed to NPFF: A transcriptional study.

Peptides 2021 02 9;136:170469. Epub 2020 Dec 9.

Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi Province, 710072, China.

Neuropeptide FF (NPFF) is a neuropeptide that modulates various physiological processes. The regulatory role of NPFF in the immune and inflammatory response is currently being revealed. However, the effect of NPFF at the transcriptome level in macrophages has not been fully elucidated. Read More

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February 2021

Correction to: The knockdown of Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion.

J Headache Pain 2020 Dec 7;21(1):140. Epub 2020 Dec 7.

Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, Chang Gung University, 259 Wenhua 1st Road, Guishan Dist, Taoyuan City, 33302, Taiwan.

An amendment to this paper has been published and can be accessed via the original article. Read More

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December 2020

Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception.

J Med Chem 2020 12 3;63(24):15709-15725. Epub 2020 Dec 3.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.

In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized. Read More

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December 2020

Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation.

Int J Mol Sci 2020 Nov 25;21(23). Epub 2020 Nov 25.

Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-105 Warsaw, Poland.

The opioid-induced analgesia is associated with a number of side effects such as addiction, tolerance and respiratory depression. The involvement of neuropeptide FF (NPFF) in modulation of pain perception, opioid-induced tolerance and dependence was well documented in contrast to respiratory depression. Therefore, the aim of the present study was to examine the potency of NPFF to block post-opioid respiratory depression, one of the main adverse effects of opioid therapy. Read More

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November 2020

Ablation of NPFFR2 in Mice Reduces Response to Single Prolonged Stress Model.

Cells 2020 11 14;9(11). Epub 2020 Nov 14.

Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 33302, Taiwan.

Mental stress is highly related to many clinical symptoms and disorders, as it activates the hypothalamic-pituitary-adrenocortical (HPA) axis to affect a wide variety of physiological functions. Furthermore, stress leads to the aberrations in HPA axis activity and disruptions of body homeostasis. It was previously shown that neuropeptide FF (NPFF) regulates the HPA axis through the activation of hypothalamus paraventricular nucleus (PVN), and genetic overexpression or pharmacological stimulation of NPFF receptor 2 (NPFFR2) triggers hyperactivity of HPA axis and suppresses behavioral correlates of emotion in mice. Read More

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November 2020

Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs.

Exp Dermatol 2020 12 29;29(12):1225-1232. Epub 2020 Oct 29.

Dermatology Department, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.

While anti-TNF therapies are effective against psoriasis, 30%-50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Read More

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December 2020

Pharmacological insight into the activation of the human neuropeptide FF2 receptor.

Peptides 2020 12 10;134:170406. Epub 2020 Sep 10.

CNRS, IPBS (Institut De Pharmacologie Et De Biologie Structurale) 205 Route De Narbonne, 31077 Toulouse, Cedex 4, France; Université Paul Sabatier Toulouse III, F-31300 Toulouse, France.

The neuropeptide FF2 (NPFF) receptor, predominantly expressed in the central nervous system, plays an important role in the modulation of sensory input and opioid analgesia, as well as in locomotion, feeding, intestinal motility, reward, and the control of obesity. The NPFF receptor belongs to the RFamide peptide receptor family and to the G protein coupled receptor (GPCR) super family, but contrary to many other class A GPCRs, no 3D structure has been solved. Thus, it is essential to perform mutagenesis to gain information on the fine functioning of the NPFF receptor. Read More

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December 2020

Characterization, Docking and Molecular Dynamics Simulation of Gonadotropin-Inhibitory Hormone Receptor (GnIHR2) in Labeo Catla.

Cell Physiol Biochem 2020 Sep;54(5):825-841

ICAR-Central Institute of Fisheries Education, Mumbai, India,

Background/aims: GnIH receptors (GnIHRs) belong to the family of G-protein coupled receptors (GPCRs) and play a key role in the regulation of reproduction from fishes to mammals, either by inhibiting or stimulating the expression of gonadotropins. The aim of this study was to characterize GnIH receptor (GnIHR2) from Indian Major Carp, Labeo catla and its docking and simulation with GnIH antagonist RF313.

Methods: The full length sequence of GnIHR2 was obtained with RACE PCR. Read More

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September 2020

Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.

J Med Chem 2020 11 31;63(21):12387-12402. Epub 2020 Jul 31.

Center for Drug Discovery, Research Triangle Institute, 3040 East Cornwallis Road, Research Triangle Park, North Carolina 27709, United States.

The endogenous neuropeptide FF (NPFF) and its two cognate G protein-coupled receptors, Neuropeptide FF Receptors 1 and 2 (NPFFR1 and NPFFR2), represent a relatively new target system for many therapeutic applications including pain regulation, modulation of opioid side effects, drug reward, anxiety, cardiovascular conditions, and other peripheral effects. Since the cloning of NPFFR1 and NPFFR2 in 2000, significant progress has been made to understand their pharmacological roles and interactions with other receptor systems, notably the opioid receptors. A variety of NPFFR ligands with different mechanisms of action (agonists or antagonists) have been discovered although with limited subtype selectivities. Read More

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November 2020

Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion.

J Headache Pain 2020 Jul 8;21(1):87. Epub 2020 Jul 8.

Graduate Institute of Biomedical Sciences, Department of Physiology and Pharmacology, Chang Gung University, 259 Wenhua 1st Road, Guishan Dist, Taoyuan City, 33302, Taiwan.

Background: Stimulation of trigeminovascular pathway is widely used to establish the headache animal model. Headache is a common neurological disorder, in which symptomatic attacks are mediated by calcitonin-gene-related peptide (CGRP). CGRP is synthesized and released from the trigeminal ganglion to transmit pain signals under stimulation. Read More

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VF-13, a chimeric peptide of VD-hemopressin(α) and neuropeptide VF, produces potent antinociception with reduced cannabinoid-related side effects.

Neuropharmacology 2020 09 13;175:108178. Epub 2020 Jun 13.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, And Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address:

Pharmacological evidence indicated a functional interaction between neuropeptide FF (NPFF) and cannabinoid systems, and the cannabinoids combined with the NPFF receptor agonist neuropeptide VF (NPVF) produced antinociception without tolerance. In the present study, VF-13, a chimeric peptide containing the pharmacophores of the endogenous cannabinoid peptide VD-hemopressin(α) (VD-Hpα) and NPVF, was synthesized and pharmacologically evaluated. In vitro, VF-13 significantly upregulated the phosphorylated level of extracellular signal-regulated kinase 1/2 (ERK1/2) in CHO cells stably expressing CB1 receptors and inhibited forskolin-induced cAMP accumulation in HEK293 cells stably expressing NPFF or NPFF receptors. Read More

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September 2020

NPFF increases fusogenic proteins syncytin 1 and syncytin 2 via GCM1 in first trimester primary human cytotrophoblast cells.

FASEB J 2020 07 5;34(7):9419-9432. Epub 2020 Jun 5.

Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

Neuropeptide FF (NPFF) is well-known for its roles in the central nervous system. Despite studies demonstrating that NPFF receptor 2 (NPFFR2) mRNA is highest in placenta, nothing is known about NPFF-NPFFR2 functions in placental development. Here, we investigated the effects of NPFF-NPFFR2 on expression of syncytial [human chorionic gonadotropin (hCG) β] and fusogenic [syncytin 1, syncytin 2, and glial cells missing 1 (GCM1)] genes in first trimester primary human cytotrophoblast cells. Read More

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Spinal administration of the multi-functional opioid/neuropeptide FF agonist BN-9 produced potent antinociception without development of tolerance and opioid-induced hyperalgesia.

Eur J Pharmacol 2020 Aug 13;880:173169. Epub 2020 May 13.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address:

Chronic opioids treatment is impeded by the development of analgesic tolerance and opioid-induced hyperalgesia. Recent studies have shown that multi-functional opioid compounds produce analgesic activities with limited side effects. We developed a novel multi-functional peptide targeting opioid and neuropeptide FF receptors named BN-9, which produced potent and non-tolerance forming antinociceptive effect after supraspinal and systemic administrations. Read More

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Central and peripheral modulation of gastrointestinal transit in mice by DN-9, a multifunctional opioid/NPFF receptor agonist.

Neurogastroenterol Motil 2020 08 12;32(8):e13848. Epub 2020 Apr 12.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Background: The nonapeptide DN-9 functions as a multifunctional agonist to opioid and neuropeptide FF (NPFF) receptors and exhibits antinociceptive effects at the central and peripheral levels.

Methods: The effects of DN-9 on small and colonic intestinal transit were evaluated using the upper gastrointestinal (GI) transit test and colonic bead expulsion assay, respectively. Opioid and NPFF receptor antagonists were used to investigate the mechanisms of DN-9-induced GI inhibition. Read More

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Characterization of the neuropeptide FF (NPFF) gene in chickens: evidence for a single bioactive NPAF peptide encoded by the NPFF gene in birds.

Domest Anim Endocrinol 2020 07 11;72:106435. Epub 2020 Jan 11.

Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China. Electronic address:

The 2 structurally related peptides, neuropeptide FF (NPFF) and neuropeptide AF (NPAF), are encoded by the NPFF gene and have been identified as neuromodulators that regulate nociception and opiate-mediated analgesia via NPFF receptor (NPFFR2) in mammals. However, little is known about these 2 peptides in birds. In this study, we examined the structure, tissue expression profile, and functionality of NPAF and NPFF in chickens. Read More

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Experimental Parasite Infection Causes Genome-Wide Changes in DNA Methylation.

Mol Biol Evol 2020 08;37(8):2287-2299

School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.

Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. Read More

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Bioanalytical method development and validation of MES207, a neuropeptide FF receptor antagonist, and its application in preclinical pharmacokinetics.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Dec 12;1134-1135:121875. Epub 2019 Nov 12.

Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA; Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

The nonpeptide small molecule, MES207, exhibits 17-fold preferential binding to the neuropeptide FF receptor 1 (NPFFR1) over NPFFR2 and shows antagonist functionality at NPFF receptors. In order to further the development of MES207 as a NPFFR1 probe, an UPLC-MS/MS bioanalytical method was developed and validated to quantify MES207 in rat plasma for a linearity range of 3-200 ng/mL. The method was applied in the analysis of the plasma, brain, and urine samples collected during pharmacokinetic studies in healthy male and female Sprague Dawley rats. Read More

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December 2019

Dynamic Changes of RFRP3/GPR147 in the Precocious Puberty Model Female Rats.

Curr Mol Med 2019 ;19(10):766-775

Traditional Chinese Medicine Department, Children's Hospital of Fudan University, Shanghai 201102, China.

Background: Pubertal development is a complex physiological process regulated by the neuroendocrine system and hypothalamic-pituitary-gonadal axis. Sexual precocity is a common childhood endocrine disease.The pathogenesis of sexual precocity has not been fully elucidated. Read More

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November 2021

Neuropeptide FF modulates neuroendocrine and energy homeostasis through hypothalamic signaling.

Chin J Physiol 2019 Mar-Apr;62(2):47-52

Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, School of Medicine; Healthy Aging Research Center, Chang Gung University; Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Neuropeptide FF (NPFF) is known as a morphine-modulating peptide and was first isolated in 1985. It has been characterized as an RF-amide peptide. The traditional role of NPFF is mediation of the pain response, and it displays both anti-opioid and pro-opioid actions through central nervous system. Read More

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