Tags

Type your tag names separated by a space and hit enter

Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors.
Neuropharmacology. 2013 Dec; 75:164-71.N

Abstract

Mammalian RF-amide peptides are encoded by five different genes and act through five different G protein-coupled receptors. RF-amide-related peptides-1 and -3, neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa peptides are currently considered endogenous peptides for NPFF1, NPFF2, GPR10, GPR54 and GPR103 receptors, respectively. However, several studies suggest that the selectivity of these peptides for their receptors is low and indicate that expression patterns for receptors and their corresponding ligands only partially overlap. In this study, we took advantage of the cloning of the five human RF-amide receptors to systematically examine their affinity for and their activation by all human RF-amide peptides. Binding experiments, performed on membranes from CHO cells expressing GPR10, GPR54 and GPR103 receptors, confirmed their high affinity and remarkable selectivity for their cognate ligands. Conversely, NPFF1 and NPFF2 receptors displayed high affinity for all RF-amide peptides. Moreover, GTPγS and cAMP experiments showed that almost all RF-amide peptides efficiently activate NPFF1 and NPFF2 receptors. As NPFF is known to modulate morphine analgesia, we undertook a systematic analysis in mice of the hyperalgesic and anti morphine-induced analgesic effects of a representative set of endogenous RF-amide peptides. All of them induced hyperalgesia and/or prevented morphine analgesia following intracerebroventricular administration. Importantly, these effects were prevented by administration of RF9, a highly selective NPFF1/NPFF2 antagonist. Altogether, our results show that all endogenous RF-amide peptides display pain-modulating properties and point to NPFF receptors as essential players for these effects.

Authors+Show Affiliations

Biotechnologie et Signalisation Cellulaire, UMR 7242 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: elhabazi@unistra.fr.Biotechnologie et Signalisation Cellulaire, UMR 7242 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: jeanpaul.humbert@aol.fr.Biotechnologie et Signalisation Cellulaire, UMR 7242 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: bertin.i@free.fr.Laboratoire Innovation Thérapeutique, UMR 7200 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: mschmitt@unistra.fr.Laboratoire Innovation Thérapeutique, UMR 7200 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: fbihel@unistra.fr.Laboratoire Innovation Thérapeutique, UMR 7200 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: jjb@unistra.fr.Laboratoire Biophotonique et Pharmacologie, UMR 7213 CNRS, Université de Strasbourg, Illkirch, France. Electronic address: bernard.bucher@unistra.fr.IGBMC, UMR 7104 CNRS, U 964 INSERM, Université de Strasbourg, Illkirch, France. Electronic address: jbecker@igbmc.fr.Institut Clinique de la Souris, PHENOMIN, IGBMC/ICS-MCI, Université de Strasbourg-CNRS-INSERM, Illkirch, France; PhenoPro, Illkirch, France. Electronic address: tsorg@igbmc.fr.Institut Clinique de la Souris, PHENOMIN, IGBMC/ICS-MCI, Université de Strasbourg-CNRS-INSERM, Illkirch, France. Electronic address: meziane@igbmc.fr.Institut Clinique de la Souris, PHENOMIN, IGBMC/ICS-MCI, Université de Strasbourg-CNRS-INSERM, Illkirch, France; PhenoPro, Illkirch, France. Electronic address: petitd@igbmc.fr.Biotechnologie et Signalisation Cellulaire, UMR 7242 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: brigitte.ilien@unistra.fr.Biotechnologie et Signalisation Cellulaire, UMR 7242 CNRS, Université de Strasbourg, Laboratory of Excellence Medalis, Illkirch, France. Electronic address: simonin@unistra.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23911743

Citation

Elhabazi, Khadija, et al. "Endogenous Mammalian RF-amide Peptides, Including PrRP, Kisspeptin and 26RFa, Modulate Nociception and Morphine Analgesia Via NPFF Receptors." Neuropharmacology, vol. 75, 2013, pp. 164-71.
Elhabazi K, Humbert JP, Bertin I, et al. Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors. Neuropharmacology. 2013;75:164-71.
Elhabazi, K., Humbert, J. P., Bertin, I., Schmitt, M., Bihel, F., Bourguignon, J. J., Bucher, B., Becker, J. A., Sorg, T., Meziane, H., Petit-Demoulière, B., Ilien, B., & Simonin, F. (2013). Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors. Neuropharmacology, 75, 164-71. https://doi.org/10.1016/j.neuropharm.2013.07.012
Elhabazi K, et al. Endogenous Mammalian RF-amide Peptides, Including PrRP, Kisspeptin and 26RFa, Modulate Nociception and Morphine Analgesia Via NPFF Receptors. Neuropharmacology. 2013;75:164-71. PubMed PMID: 23911743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors. AU - Elhabazi,Khadija, AU - Humbert,Jean-Paul, AU - Bertin,Isabelle, AU - Schmitt,Martine, AU - Bihel,Frédéric, AU - Bourguignon,Jean-Jacques, AU - Bucher,Bernard, AU - Becker,Jérôme A J, AU - Sorg,Tania, AU - Meziane,Hamid, AU - Petit-Demoulière,Benoit, AU - Ilien,Brigitte, AU - Simonin,Frédéric, Y1 - 2013/08/02/ PY - 2013/05/22/received PY - 2013/07/15/revised PY - 2013/07/16/accepted PY - 2013/8/6/entrez PY - 2013/8/6/pubmed PY - 2014/8/20/medline KW - AUC KW - GPR10 KW - GPR103 KW - GPR54 KW - Kp KW - NPAF KW - NPFF KW - NPFF receptors KW - NPSF KW - NPVF KW - Nociception and morphine analgesia KW - PrRP KW - RF-amide peptides KW - RF-amide-related peptide KW - RFRP KW - area-under-the-curve KW - i.c.v. KW - i.t. KW - intracerebroventricular KW - intrathecal KW - kisspeptin KW - neuropeptide AF KW - neuropeptide FF KW - neuropeptide SF KW - neuropeptide VF KW - prolactin releasing peptide SP - 164 EP - 71 JF - Neuropharmacology JO - Neuropharmacology VL - 75 N2 - Mammalian RF-amide peptides are encoded by five different genes and act through five different G protein-coupled receptors. RF-amide-related peptides-1 and -3, neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa peptides are currently considered endogenous peptides for NPFF1, NPFF2, GPR10, GPR54 and GPR103 receptors, respectively. However, several studies suggest that the selectivity of these peptides for their receptors is low and indicate that expression patterns for receptors and their corresponding ligands only partially overlap. In this study, we took advantage of the cloning of the five human RF-amide receptors to systematically examine their affinity for and their activation by all human RF-amide peptides. Binding experiments, performed on membranes from CHO cells expressing GPR10, GPR54 and GPR103 receptors, confirmed their high affinity and remarkable selectivity for their cognate ligands. Conversely, NPFF1 and NPFF2 receptors displayed high affinity for all RF-amide peptides. Moreover, GTPγS and cAMP experiments showed that almost all RF-amide peptides efficiently activate NPFF1 and NPFF2 receptors. As NPFF is known to modulate morphine analgesia, we undertook a systematic analysis in mice of the hyperalgesic and anti morphine-induced analgesic effects of a representative set of endogenous RF-amide peptides. All of them induced hyperalgesia and/or prevented morphine analgesia following intracerebroventricular administration. Importantly, these effects were prevented by administration of RF9, a highly selective NPFF1/NPFF2 antagonist. Altogether, our results show that all endogenous RF-amide peptides display pain-modulating properties and point to NPFF receptors as essential players for these effects. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/23911743/Endogenous_mammalian_RF_amide_peptides_including_PrRP_kisspeptin_and_26RFa_modulate_nociception_and_morphine_analgesia_via_NPFF_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(13)00329-8 DB - PRIME DP - Unbound Medicine ER -