Pharmacological characterization of human NPFF1 and NPFF2 receptors expressed in CHO cells by using NPY Y1 receptor antagonists

Mollereau, Catherine; Mazarguil, Honoré; Marcus, Delphine; Quelven, Isabelle; Kotani, Masato; Lannoy, Vincent; Dumont, Yvan; Quirion, Rémi; Detheux, Michel; Parmentier, Marc; Zajac, Jean‐Marie

doi:10.1016/s0014-2999(02)02224-0

Cited by 129 publications

(137 citation statements)

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“…NPSF has almost equal affinity for GPR74 and GPR147, whereas NPFF has at least 10 times higher affinity for the former receptor. 10,13,14 Our results suggest that the two receptors mediate different effects on lipolysis. NPFF has no effect on catecholamineinduced lipolysis using the natural ligand noradrenaline alone.…”

Section: Discussionmentioning

confidence: 65%

“…Detailed examinations of signal transduction can only be carried out in cell systems with stable manipulation of the expression of either or both of the receptors. [5][6][7][8][9]13,14 Unfortunately at present it is not possible to carry out such studies in human adipocytes kept in primary culture. We therefore used an indirect approach by comparing the effect of NPFF with that of NPSF and by using selective lipolysis agents acting on defined steps in signal transduction.…”

Section: Discussionmentioning

confidence: 99%

“…NPFF has higher affinity for binding to GPR74 than for GPR147, whereas NPSF has equal binding affinity for GPR74 and GPR147. 10,13,14 Our primary hypothesis was that these neuropeptides are regulators of human fat cell lipolysis, which is achieved by interacting with their target receptors. The second hypothesis was that the neuropeptide regulation of lipolysis is influenced by obesity.…”

Section: Introductionmentioning

confidence: 99%

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Effects of pain controlling neuropeptides on human fat cell lipolysis

et al. 2010

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Objective: Neuropeptides NPFF and NPSF are involved in pain control, acting through the G-protein coupled receptors (GPR)74 (high affinity for NPFF) and GPR147 (equal affinity for NPFF and NPSF). GPR74 also inhibits catecholamine-induced adipocyte lipolysis and regulates fat mass in humans. The aim of this study was to compare the effects of NPFF and NPSF on noradrenalineinduced lipolysis and to determine the expression of their receptors in human fat cells. Design: Adipose tissue was obtained during surgery. Adipocytes were prepared and kept in primary culture. Lipolysis, protein expression and gene expression were determined. Results: NPFF counteracted noradrenaline-induced lipolysis, which was more marked after 48 h than after 4 h exposure and was solely attributed to inhibition of b-adrenoceptor signalling. NPSF counteracted noradrenaline-induced lipolysis maximally after 4 h of exposure, which was attributed to a combination of inhibition of b-adrenoceptor signalling and decreased activation of the protein kinase-A hormone sensitive lipase complex by cyclic AMP. Both neuropeptides were effective in nanomolar concentrations. NPFF and NPSF had no effects on the expression of genes involved in catecholamine signal transduction. Both GPR74 and GPR147 were expressed at the protein level in fat cells from various adipose regions. GPR74 mRNA levels were higher in adipose tissue from obese as compared with non-obese subjects. High gene expression of either receptor correlated with low noradrenaline-induced lipolysis (Po0.05). Conclusions: Pain controlling neuropeptides NPFF and NPSF may be important for the regulation of lipolysis in man probably acting through GPR74 and GPR147. At low concentrations they inhibit catecholamine-induced lipolysis through rapid and longterm post-transcriptional effects at several steps in adrenoceptor signalling in fat cells.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of pain controlling neuropeptides on human fat cell lipolysis

et al. 2010

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“…This study exemplified that on-line capillary HPLC/ nanospray ion trap tandem mass spectrometry was a powerful analytical technique, giving rise to the characterization of minute amounts of endogenous neuropeptides [32]. The physiological relevance of these observations is that the three peptides, NPFF, SQA-NPFF and hNPAF, could act as neurotransmitters in human as they exhibit a high affinity and a high activity towards NPFF 2 receptors [26,42]. We have compared previously the affinities and antiopioid activities of the different peptides putatively produced by the rat NPFF precursor and reveal that the undecapeptides are likely to be the physiologically active neurotransmitters in brain as they exhibit high affinity for NPFF 2 receptor, functional activity and they could be generated from proNPFF A precursor in neuronal cells.…”

Section: Discussionmentioning

confidence: 86%

“…Pharmacological characterization of these receptors in recombinant cell lines showed a better selectivity of peptides deduced from proNPFF A sequence for NPFF 2 receptors binding, whereas proN-PFF B -derived peptides displayed a greater affinity for NPFF 1 receptors [26]. Autoradiographic studies performed on rat CNS with highly selective radioligands revealed the localization of both receptors in central nervous areas implicated in pain transmission [27].…”

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confidence: 99%

Identification of proNeuropeptide FF_A peptides processed in neuronal and non‐neuronal cells and in nervous tissue

Bonnard

Burlet‐Schiltz

Monsarrat

et al. 2003

European Journal of Biochemistry

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Peptides which should be generated from the neuropeptide FF (NPFF) precursor were identified in a neuronal (human neuroblastoma SH-SY5Y) cell line and in COS-7 cells after transient transfection of the human proNPFF A cDNA and were compared with those detected in the mouse spinal cord. After reverse-phase high performance liquid chromatography of soluble material, NPFF-related peptides were immunodetected with antisera raised against NPFF and identified by using on-line capillary liquid chromatography/ nanospray ion trap tandem mass spectrometry. Neuronal and non-neuronal cells generated different peptides from the same precursor. In addition to NPFF, SQA-NPFF (Ser-Gln-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide) and NPAF were identified in the human neuroblastoma while only NPFF was clearly identified in COS-7 cells. In mouse, in addition to previously detected NPFF and NPSF, SPA-NPFF (Ser-Pro-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Pheamide), the homologous peptide of SQA-NPFF, were characterized. These data on intracellular processing of proNeuropeptide FFA are discussed in regard to the known enzymatic processing mechanisms. There is a large body of evidence that NPFF exhibits antiopioid properties; in rodents, morphine-induced analgesia decreased following administration of NPFF or NPFF analogues and increased, as stress-induced analgesia, in response to anti-NPFF antibody administration [6][7][8]. In contrast, intrathecal injections of NPFF analogues induced a long-lasting analgesia [9,10] by increasing opioid peptide release in the spinal cord through the functional blockade of presynaptic delta-opioid autoreceptors [11,12]. Recent data provided evidence that opioid and NPFF endogenous systems exert a tonic activity, NPFF counteracting tonic opioid analgesia under resting conditions [13]. NPFF is also implicated in morphine tolerance, morphine abstinence and also in several physiological processes, such as body thermoregulation, food intake and blood pressure regulation [7,[14][15][16][17][18][19][20][21].These pharmacological effects are mediated by two G-protein-coupled receptors, NPFF 1 and NPFF 2 , cloned in human and rat [22][23][24][25]. Pharmacological characterization of these receptors in recombinant cell lines showed a better selectivity of peptides deduced from proNPFF A sequence for NPFF 2 receptors binding, whereas proN-PFF B -derived peptides displayed a greater affinity for NPFF 1 receptors [26]. Autoradiographic studies performed on rat CNS with highly selective radioligands revealed the localization of both receptors in central nervous areas implicated in pain transmission [27]. The existence of two peptidergic systems of neurotransmission, mediated through NPFF 1 and NPFF 2 receptor stimulation by peptides generated by proNPFF B and proNPFF A processing, respectively, could explain the complex pharmacological effects of NPFF.The characterization of NPFF-related peptides generated by NPFF precursors processing is essential to identify peptides candidate to the role of neurotransmitter. This study f...

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Neuropeptide AF Induces Piecemeal Degranulation in Murine Mucosal Mast Cells: A New Mediator in Neuro‐Immune Communication in the Intestinal Lamina Propria?

Abdellah

Remoortel

Mohey-Elsaeed

et al. 2018

The Anatomical Record

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Neuropeptides AF (NPAF), FF (NPFF) and SF (NPSF) are RFamide neuropeptides known to be widely expressed in the mammalian central nervous system, where they fulfill a wide range of functions with pain modulation being the most prominent one. Recent evidence indicates that RFamides act as mediators in mast cell–sensory nerve communications related to allergic disease. Previous work by our group has shown that the expression levels of some members of the Mas‐related gene receptor (Mrgpr) family in both enteric neurons and mucosal mast cells change during intestinal inflammation. The Mrgpr subtypes C11 and A4 can be activated by NPAF, while A1 and C11 are triggered by NPFF. The aim of the present study was to investigate whether RFamides of the NPFF group are expressed in the gastrointestinal tract and to identify possible targets and receptors that might be involved in RFamide‐associated mast cell modulation. To this end, the expression and distribution patterns of NPFF/AF receptors and the NPFF precursor protein were determined in bone marrow‐derived mucosal mast cells (BMMCs) by immunocytochemistry and (RT‐) PCR. BMMCs were found to express MrgprA4 and A1, and functional analysis of the effects of NPAF by means of a β‐hexosaminidase assay, mMCP‐1 ELISA, electron microscopy and live cell calcium imaging revealed a piecemeal degranulation induced by NPAF. However, knock‐out of MrgprA4 and A1 did not reduce the effect of NPAF, indicating that the BMMC response to NPAF was receptor independent. ProNPFF was expressed in neurons and BMMCs, suggesting that both cell types are potential sources of NPAF in situ. Our results show that the RFamide NPAF can be considered as a novel modulator of BMMC activity in the neuro‐immune communication in the gastrointestinal tract, although the exact signaling pathway remains to be elucidated. Anat Rec, 00:000–000, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 301:1103–1114, 2018. © 2018 Wiley Periodicals, Inc.

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Pharmacological characterization of human NPFF1 and NPFF2 receptors expressed in CHO cells by using NPY Y1 receptor antagonists

Cited by 129 publications

References 42 publications

Effects of pain controlling neuropeptides on human fat cell lipolysis

Effects of pain controlling neuropeptides on human fat cell lipolysis

Identification of proNeuropeptide FF_A peptides processed in neuronal and non‐neuronal cells and in nervous tissue

Neuropeptide AF Induces Piecemeal Degranulation in Murine Mucosal Mast Cells: A New Mediator in Neuro‐Immune Communication in the Intestinal Lamina Propria?

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Pharmacological characterization of human NPFF1 and NPFF2 receptors expressed in CHO cells by using NPY Y1 receptor antagonists

Cited by 129 publications

References 42 publications

Effects of pain controlling neuropeptides on human fat cell lipolysis

Effects of pain controlling neuropeptides on human fat cell lipolysis

Identification of proNeuropeptide FFA peptides processed in neuronal and non‐neuronal cells and in nervous tissue

Neuropeptide AF Induces Piecemeal Degranulation in Murine Mucosal Mast Cells: A New Mediator in Neuro‐Immune Communication in the Intestinal Lamina Propria?

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Identification of proNeuropeptide FF_A peptides processed in neuronal and non‐neuronal cells and in nervous tissue