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12 results on '"MESH: Receptors, Neuropeptide"'

1. Contribution of functionally assessed GHRHR mutations to idiopathic isolated growth hormone deficiency in patients without GH1 mutations

Author

Merih Berberoğlu, Régis Coutant, Şenay Savaş Erdeve, Cécile Brachet, Caroline Thalassinos, Frédéric Brioude, Michel Polak, Erdal Kurnaz, Sabrina Belkacem, Claudine Heinrichs, Aude Soleyan, Zeynep Şıklar, Nathalie Collot, Philippe Chanson, Jean-Claude Carel, Zehra Aycan, Marie-Laure Sobrier, Serge Amselem, Géraldine Viot, Noureddine Kaffel, Stanislas Lyonnet, Philippe Duquesnoy, Eliane Khallouf, Marie Legendre, Enzo Cohen, Soumeya Fedala, Sophie Rose, Florence Dastot, Frédérique Gatelais, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lamine Debaghine [Alger, Algérie] (HLD), Centre Hospitalier Universitaire Bab El Oued [Alger, Algérie] (CHU Bab El Oued), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux Universitaires Paris Centre (CHU Paris Centre), Hôpital Robert Debré, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Brussels, Belgium]. (HUERF), Complexe Médical Multidisciplinaire [Sfax, Tunisia] (C2M), Ankara University School of Medicine [Turkey], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Dupuis, Christine, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des maladies génétiques d'expression pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service de Génétique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], AP-HP Hôpital universitaire Robert-Debré [Paris], Hôpital Universitaire des Enfants Reine Fabiola, Université libre de Bruxelles (ULB), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Division of Paediatric Endocrinology, Dr Sami Ulus Woman Health, Children Research Hospital, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Children's University Hospital Queen Fabiola [Bruxelles, Belgium], Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Receptors, Neuropeptide, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, MESH: Amino Acid Sequence, medicine.disease_cause, molecular epidemiology, MESH: Genotype, Exon, Receptors, Pituitary Hormone-Regulating Hormone, Cyclic AMP, IGHD, MESH: Human Growth Hormone, Missense mutation, MESH: DNA Mutational Analysis, Idiopathic Isolated Growth Hormone Deficiency, Genetics (clinical), genotype‐phenotype correlation, MESH: Cyclic AMP, MESH: Genetic Association Studies, Genetics, 0303 health sciences, Mutation, Human Growth Hormone, MESH: Receptors, Neuropeptide, 030305 genetics & heredity, MESH: Genetic Predisposition to Disease, MESH: Amino Acid Substitution, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], functional studies, Female, MESH: Mutation, Genotype, MESH: Pedigree, Genetic counseling, GHRHR, Biology, genotype-phenotype correlation, MESH: Dwarfism, Pituitary, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Dwarfism, Pituitary, Gene, Alleles, Genetic Association Studies, 030304 developmental biology, MESH: Humans, Molecular epidemiology, MESH: Receptors, Pituitary Hormone-Regulating Hormone, MESH: Alleles, MESH: Male, Amino Acid Substitution, MESH: Female
Abstract

International audience; Isolated growth hormone deficiency (IGHD) is a rare condition mainly caused by mutations in GH1. The aim of this study was to assess the contribution of GHRHR mutations to IGHD in an unusually large group of patients. All GHRHR coding exons and flanking intronic regions were sequenced in 312 unrelated patients with nonsyndromic IGHD. Functional consequences of all newly identified missense variants were assessed in vitro (i.e., study of the expression of recombinant GHRHRs and their ability to activate the cyclic adenosine monophosphate (cAMP) signaling pathway). Genotype-phenotype correlation analyses were performed according to the nature of the identified mutation. We identified 20 different disease-causing GHRHR mutations (truncating and missense loss-of-function mutations), among which 15 are novel, in 24 unrelated patients. Of note, about half (13/24) of those patients represent sporadic cases. The clinical phenotype of patients with at least one missense GHRHR mutation was found to be indistinguishable from that of patients with bi-allelic truncating mutations. This study, which unveils disease-causing GHRHR mutations in 8% (24/312) of IGHD cases, identifies GHRHR as the second IGHD gene most frequently involved after GH1. The finding that 8% of IGHD cases without GH1 mutations are explained by GHRHR molecular defects (including missense mutations), together with the high proportion of sporadic cases among those patients, has important implications for genetic counseling.

Published
2019

2. The Arg-Phe-amide peptide 26RFa/glutamine RF-amide peptide and its receptor: IUPHAR Review 24

Author

Leprince, Jérôme, Bagnol, Didier, Bureau, Ronan, Fukusumi, Shoji, Granata, Riccarda, Hinuma, Shuji, Larhammar, Dan, Primeaux, Stefany, Sopkova‐de Oliveiras Santos, Jana, Tsutsui, Kazuyoshi, Ukena, Kazuyoshi, Vaudry, Hubert, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), ARENA Pharmaceuticals, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université de Tsukuba = University of Tsukuba, Università degli studi di Torino (UNITO), Osaka University [Osaka], Uppsala University, Louisiana State University (LSU), Waseda University, and Hiroshima University

Subjects
Receptors, Neuropeptide, MESH: Humans, MESH: Peptides, MESH: Receptors, Neuropeptide, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuropeptides, IUPHAR Review, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Animals, Humans, Intercellular Signaling Peptides and Proteins, MESH: Animals, Peptides
Abstract

International audience; 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.

Published
2017

3. Decreased motivational properties of morphine in mouse models of cancerous- or inflammatory-chronic pain: Implication of supraspinal neuropeptide FF2 receptors

Author

Alexandre Betourne, Julien Familiades, Hélène Halley, Ludovic Lacassagne, Jean-Marie Zajac, Bernard Frances, Martine Cazales, Jean-Michel Lassalle, Bernard Ducommun, Centre de Recherches sur la Cognition Animale (CRCA), Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut d'électronique fondamentale (IEF), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Conditioned Place Preference, Receptors, Neuropeptide, MESH: Inflammation, cancer pain, MESH: Conditioning, Operant, MESH: Pain Measurement, Pharmacology, MESH: Analgesics, Opioid, Mice, MESH: Autoradiography, 0302 clinical medicine, Neoplasms, MESH: Behavior, Animal, Edema, Medicine, MESH: Animals, MESH: Neoplasms, Key words: Neuropeptide FF, Neuropeptide FF, reward, inflammatory pain, Pain Measurement, 0303 health sciences, Behavior, Animal, Morphine, MESH: Receptors, Neuropeptide, General Neuroscience, Chronic pain, MESH: Motor Activity, 3. Good health, Analgesics, Opioid, MESH: Edema, Islands of Calleja, Female, MESH: Pain, medicine.drug, Agonist, medicine.drug_class, MESH: Motivation, Pain, Motor Activity, Nucleus accumbens, MESH: Foot, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Animals, MESH: Mice, 030304 developmental biology, Inflammation, Motivation, Foot, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, MESH: Chronic Disease, medicine.disease, Conditioned place preference, Mice, Inbred C57BL, MESH: Morphine, Chronic Disease, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Autoradiography, Conditioning, Operant, business, Cancer pain, MESH: Female, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Our main purpose was to evaluate the influence of cancer pain on the rewarding properties of morphine. Opioids are very addictive when used by healthy persons, conversely the occurrence of an opioid addiction seems very low when patients suffering from cancer are treated with morphine. We investigated the reinforcing properties of morphine in the place preference paradigm on a new model of mice suffering from a cancer pain induced by syngenic melanoma cells injected in the hind paw. These data were compared with mice suffering either from a short-term- or a chronic-inflammatory pain induced respectively by injection of carrageenan or complete Freund's adjuvant. Remarkably, mice suffering from cancer pain or chronic inflammatory pain did not develop any preference for the environment associated with the injection of morphine. In mice injected with melanoma cells, the specific binding of [(125)I]EYWSLAAPQRF-NH(2), an agonist of neuropeptide FF(2) receptors, was increased in several brain areas involved in the rewarding properties of opiates, including the shell of the nucleus accumbens, the major islands of Calleja, the ventral endopiriform nucleus and the amygdaloid area. Our study is the first to reveal a modification of morphine rewarding properties under cancer pain in rodents. We postulate that anti-opioid neuropeptides might contribute to the suppression of morphine rewarding effects in this murine model of cancer pain.

Published
2008

4. Neuropeptide FF-sensitive confinement of mu opioid receptor does not involve lipid rafts in SH-SY5Y cells

Author

Lionel Moulédous, Jérémie Neasta, Soren Merker, Jean-Marie Zajac, Catherine Mollereau, Benoît Roux, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and ANR-06-NEUR-0041,Pain and RF-amides,Rôle des récepteurs de neuropeptides RF-amides mammifères dans la modulation de la douleur et la tolérance aux effets analgésiques des opiacés.(2006)

Subjects
Receptors, Neuropeptide, SH-SY5Y, Detergents, Biophysics, Receptors, Opioid, mu, MESH: Membrane Microdomains, Neuropeptide FF receptor, MESH: Receptors, Opioid, mu, Cell Fractionation, Biochemistry, Cell Line, 03 medical and health sciences, Membrane Microdomains, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Neuropeptide FF, Receptor, Molecular Biology, Lipid raft, 030304 developmental biology, 0303 health sciences, MESH: Humans, Chemistry, MESH: Receptors, Neuropeptide, 030302 biochemistry & molecular biology, Fluorescence recovery after photobleaching, Cell Biology, MESH: Cell Line, MESH: Oligopeptides, MESH: Cell Fractionation, Cell fractionation, μ-opioid receptor, Oligopeptides, MESH: Fluorescence Recovery After Photobleaching, Fluorescence Recovery After Photobleaching, MESH: Detergents
Abstract

Mu opioid (MOP) receptor activation can be functionally modulated by stimulation of Neuropeptide FF 2 (NPFF(2)) G protein-coupled receptors. Fluorescence recovery after photobleaching experiments have shown that activation of the NPFF(2) receptor dramatically reduces the fraction of MOP receptors confined in microdomains of the plasma membrane of SH-SY5Y neuroblastoma cells. The aim of the present work was to assess if the direct observation of receptor compartmentation by fluorescence techniques in living cells could be related to indirect estimation of receptor partitioning in lipid rafts after biochemical fractionation of the cell. Our results show that MOP receptor distribution in lipid rafts is highly dependent upon the method of purification, questioning the interpretation of previous data regarding MOP receptor compartmentation. Moreover, the NPFF analogue 1DMe does not modify the distribution profile of MOP receptors, clearly demonstrating that membrane fractionation data do not correlate with direct measurement of receptor compartmentation in living cells.

Published
2008

5. Characterization of Sleep in Zebrafish and Insomnia in Hypocretin Receptor Mutants

Author

Tohei Yokogawa, Philippe Mourrain, Frédéric M. Rosa, Jian-Jian Zhang, Guillaume Pézeron, Wilfredo Marin, Emmanuel Mignot, Lior Appelbaum, Juliette Faraco, Howard Hughes Medical Institute (HHMI), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Génétique moléculaire du développement, Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-IFR36-Institut National de la Santé et de la Recherche Médicale (INSERM), This research was funded by the McKnight Foundation and the Howard Hughes Medical Research Institute., Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), and Autard, Delphine

Subjects
Receptors, Neuropeptide, Cataplexy, Light, MESH: Amino Acid Sequence, MESH: Receptors, G-Protein-Coupled, MESH: Neuropeptides, Receptors, G-Protein-Coupled, 0302 clinical medicine, MESH: Biogenic Monoamines, Orexin Receptors, Sleep Initiation and Maintenance Disorders, MESH: Behavior, Animal, Homeostasis, MESH: Animals, Biology (General), Neuroscience of sleep, Zebrafish, 0303 health sciences, Behavior, Animal, MESH: Receptors, Neuropeptide, General Neuroscience, Intracellular Signaling Peptides and Proteins, Brain, MESH: Sleep Deprivation, Sleep in non-human animals, Orexin receptor, MESH: Homeostasis, Synopsis, medicine.symptom, General Agricultural and Biological Sciences, Arousal, Research Article, medicine.medical_specialty, MESH: Sleep, QH301-705.5, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Zebrafish Proteins, Biology, Neurological Disorders, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, MESH: Brain, MESH: Sleep Initiation and Maintenance Disorders, Internal medicine, MESH: Intracellular Signaling Peptides and Proteins, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biogenic Monoamines, Amino Acid Sequence, MESH: Zebrafish, 030304 developmental biology, Orexins, MESH: Molecular Sequence Data, MESH: Humans, General Immunology and Microbiology, MESH: Arousal, Neuropeptides, Genetics and Genomics, Zebrafish Proteins, medicine.disease, biology.organism_classification, MESH: Light, Orexin, Sleep deprivation, Endocrinology, Sleep Deprivation, Sleep, Neuroscience, Sequence Alignment, 030217 neurology & neurosurgery, Narcolepsy
Abstract

Sleep is a fundamental biological process conserved across the animal kingdom. The study of how sleep regulatory networks are conserved is needed to better understand sleep across evolution. We present a detailed description of a sleep state in adult zebrafish characterized by reversible periods of immobility, increased arousal threshold, and place preference. Rest deprivation using gentle electrical stimulation is followed by a sleep rebound, indicating homeostatic regulation. In contrast to mammals and similarly to birds, light suppresses sleep in zebrafish, with no evidence for a sleep rebound. We also identify a null mutation in the sole receptor for the wake-promoting neuropeptide hypocretin (orexin) in zebrafish. Fish lacking this receptor demonstrate short and fragmented sleep in the dark, in striking contrast to the excessive sleepiness and cataplexy of narcolepsy in mammals. Consistent with this observation, we find that the hypocretin receptor does not colocalize with known major wake-promoting monoaminergic and cholinergic cell groups in the zebrafish. Instead, it colocalizes with large populations of GABAergic neurons, including a subpopulation of Adra2a-positive GABAergic cells in the anterior hypothalamic area, neurons that could assume a sleep modulatory role. Our study validates the use of zebrafish for the study of sleep and indicates molecular diversity in sleep regulatory networks across vertebrates., Author Summary Sleep disorders are common and poorly understood. Further, how and why the brain generates sleep is the object of intense speculations. In this study, we demonstrate that a bony fish used for genetic studies sleeps and that a molecule, hypocretin, involved in causing narcolepsy, is conserved. In humans, narcolepsy is a sleep disorder associated with sleepiness, abnormal dreaming, and paralysis and insomnia. We generated a mutant fish in which the hypocretin system was disrupted. Intriguingly, this fish sleep mutant does not display sleepiness or paralysis but has a 30% reduction of its sleep time at night and a 60% decrease in sleep bout length compared with non-mutant fish. We also studied the relationships between the hypocretin system and other sleep regulatory brain systems in zebrafish and found differences in expression patterns in the brain that may explain the differences in behavior. Our study illustrates how a sleep regulatory system may have evolved across vertebrate phylogeny. Zebrafish, a powerful genetic model that has the advantage of transparency to study neuronal networks in vivo, can be used to study sleep., Zebrafish sleep, and have the receptor for the wake-inducing molecule hypocretin. While mutation in this receptor causes narcolepsy in mammals, in fish, sleep is fragmented, demonstrating differences in sleep control in vertebrates.

Published
2007

6. Functional differences between NPFF1 and NPFF2 receptor coupling: High intrinsic activities of RFamide-related peptides on stimulation of [35S]GTPγS binding

Author

Gouardères, N, Mazarguil, H., Mollereau, C., Chartrel, N., Leprince, Jérôme, Vaudry, H., Zajac, J-M, Gouardères, C., Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
Receptors, Neuropeptide, MESH: Drug Interactions, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Cricetinae, Stimulation, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Isotopes, MESH: Cricetulus, Cricetinae, MESH: Radionuclide Imaging, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Drug Interactions, MESH: Animals, Neuropeptide FF, Receptor, chemistry.chemical_classification, 0303 health sciences, MESH: Receptors, Neuropeptide, Chinese hamster ovary cell, MESH: GTP-Binding Protein alpha Subunits, GTP-Binding Protein alpha Subunits, Biochemistry, MESH: Guanosine 5'-O-(3-Thiotriphosphate), Protein Binding, MESH: Isotopes, G protein, CHO Cells, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cricetulus, MESH: CHO Cells, Animals, Humans, MESH: Protein Binding, Radionuclide Imaging, 030304 developmental biology, Pharmacology, MESH: Humans, Dose-Response Relationship, Drug, Cell Membrane, Neuropeptides, MESH: Saponins, Saponins, Gtpγs binding, chemistry, Guanosine 5'-O-(3-Thiotriphosphate), Biophysics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030217 neurology & neurosurgery, Low sodium, MESH: Cell Membrane
Abstract

International audience; By using an optimized [(35)S]GTPgammaS binding assay, the functional activities (potency and efficacy) of peptides belonging to three members of the RFamide family; Neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and 26RFamide, were investigated on NPFF(1) and NPFF(2) receptors stably expressed in Chinese Hamster Ovary (CHO) cells. Despite their large differences in affinity and selectivity, all analogues tested behaved as agonists toward NPFF(1) and NPFF(2) receptors. High NaCl concentration in the assay strongly increased the efficacy toward NPFF(2) receptors and augmented differences among agonists. In low sodium conditions, whereas the potencies of agonists correlated with their affinities for NPFF(1) receptors, NPFF(2) receptors exhibited an extraordinary activity since all compounds tested displayed EC(50) values of GTPgammaS binding lower than their K(I) values. Comparisons of functional values between NPFF(1) and NPFF(2) receptors revealed unexpected potent selective NPFF(2) agonists especially for the PLRFamide and the VGRFamide sequences. By using blocker peptides, we also show that Galpha(i3) and Galpha(s) are the main transducers of NPFF(1) receptors while NPFF(2) are probably coupled with Galpha(i2), Galpha(i3), Galpha(o) and Galpha(s) proteins. Our data indicate that NPPF(1) and NPFF(2) receptors are differently coupled to G proteins in CHO cells.

Published
2007

7. Pharmacological characterization of the receptor mediating the anorexigenic action of the octadecaneuropeptide: evidence for an endozepinergic tone regulating food intake

Author

do Rego, Jean, Orta, Marie-Hélène, Leprince, Jérôme, Tonon, Marie-Christine, Vaudry, Hubert, Costentin, Jean, Do Rego, Jean-Claude, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Neuropsycho-pharmacologie expérimentale, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Service Commun d'Analyse Comportementale (SCAC), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Flumazenil, Male, Receptors, Neuropeptide, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Appetite, MESH: Receptors, G-Protein-Coupled, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, MESH: Neuropeptides, MESH: Dose-Response Relationship, Drug, Receptors, G-Protein-Coupled, chemistry.chemical_compound, Mice, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Receptor, MESH: Peptide Fragments, MESH: Receptors, GABA-A, MESH: Flumazenil, MESH: GABA-A Receptor Antagonists, 2. Zero hunger, Diazepam Binding Inhibitor, 0303 health sciences, Chemistry, GABAA receptor, MESH: Peptides, MESH: Receptors, Neuropeptide, hemic and immune systems, respiratory system, Receptor antagonist, MESH: Motor Activity, 3. Good health, Anorexia, Psychiatry and Mental health, medicine.drug, Agonist, medicine.medical_specialty, Endozepine, medicine.drug_class, Hypothalamus, Motor Activity, MESH: Food Deprivation, 03 medical and health sciences, Internal medicine, medicine, MESH: Isoquinolines, Animals, GABA-A Receptor Antagonists, GABA Modulators, MESH: Mice, 030304 developmental biology, Dose-Response Relationship, Drug, Appetite Regulation, Neuropeptides, Antagonist, Isoquinolines, Receptors, GABA-A, MESH: Hypothalamus, MESH: Male, Peptide Fragments, Metabotropic receptor, Endocrinology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, MESH: Anorexia, MESH: Appetite, Food Deprivation, Peptides, 030217 neurology & neurosurgery, MESH: GABA Modulators, MESH: Appetite Regulation
Abstract

International audience; Peptides of the endozepine family, including diazepam-binding inhibitor, the triakontatetraneuropeptide, and the octadecaneuropeptide (ODN), act through three types of receptors, that is, central-type benzodiazepine receptors (CBR), peripheral-type (mitochondrial) benzodiazepine receptors (PBR) and a metabotropic receptor positively coupled to phospholipase C via a pertussis toxin-sensitive G protein. We have previously reported that ODN exerts a potent anorexigenic effect in rat and we have found that the action of ODN is not affected by the mixed CBR/PBR agonist diazepam. In the present report, we have tested the possible involvement of the metabotropic receptor in the anorexigenic activity of ODN. Intracerebroventricular administration of the C-terminal octapeptide (OP) and its head-to-tail cyclic analog cyclo(1-8)OP (cOP) at a dose of 100 ng mimicked the inhibitory effect of ODN on food intake in food-deprived mice. The specific CBR antagonist flumazenil and the PBR antagonist PK11195 did not prevent the effect of ODN, OP, and cOP on food consumption. In contrast, the selective metabotropic endozepine receptor antagonist cyclo(1-8)[DLeu(5)]OP (100-1000 ng; cDLOP) suppressed the anorexigenic effect of ODN, OP, and cOP. At the highest concentration tested (1000 ng), cDLOP provoked by itself a significant increase in food intake. Taken together, the present results indicate that the anorexigenic effect of ODN and OP is mediated through activation of the metabotropic receptor recently characterized in astrocytes. The data also suggest that endogenous ODN, acting via this receptor, exerts an inhibitory tone on feeding behavior.

Published
2006

8. Excitatory action of hypocretin/orexin on neurons of the central medial amygdala

Author

A. Bisetti, Mauro Serafin, Laurence Bayer, Danièle Machard, V. Cvetkovic, Michel Muhlethaler, Barbara E. Jones, Laboratoire de Neurobiologie des Réseaux Sensorimoteurs (LNRS), Université Paris Diderot - Paris 7 (UP7) - Université Paris Descartes - Paris 5 (UPD5), and Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Amygdala/drug effects/ metabolism, Receptors, Neuropeptide, Receptors, Vasopressin, Potassium Channels, Lateral hypothalamus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neurons, MESH: Fear, Action Potentials, MESH: Receptors, G-Protein-Coupled, MESH: Neuropeptides, Synaptic Transmission, Arousal/drug effects/physiology, Receptors, G-Protein-Coupled, 0302 clinical medicine, Postsynaptic potential, Orexin Receptors, MESH: Amygdala, Neural Pathways, MESH: Animals, Excitatory Postsynaptic Potentials/drug effects/ physiology, MESH: Action Potentials, Neurons, 0303 health sciences, MESH: Receptors, Neuropeptide, General Neuroscience, Intracellular Signaling Peptides and Proteins, MESH: Stress, Psychological, MESH: Potassium Channels, Fear, Neurons/drug effects/ metabolism, Amygdala, Orexin receptor, medicine.anatomical_structure, Hypothalamus, Excitatory postsynaptic potential, MESH: Receptors, Vasopressin, Psychology, Arousal, MESH: Vasopressins, medicine.medical_specialty, Receptors, G-Protein-Coupled/drug effects/metabolism, Synaptic Transmission/drug effects/ physiology, MESH: Rats, Vasopressins, Neuropeptides/ metabolism/pharmacology, 03 medical and health sciences, Organ Culture Techniques, MESH: Intracellular Signaling Peptides and Proteins, Internal medicine, MESH: Synaptic Transmission, medicine, Animals, MESH: Excitatory Postsynaptic Potentials, Neural Pathways/drug effects/ metabolism, Stress, Psychological/metabolism/physiopathology, 030304 developmental biology, Receptors, Neuropeptide/drug effects/metabolism, Orexins, Vasopressins/metabolism/pharmacology, MESH: Arousal, MESH: Neural Pathways, Neuropeptides, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Excitatory Postsynaptic Potentials, MESH: Organ Culture Techniques, ddc:616.8, Potassium Channels/drug effects/metabolism, Orexin, Rats, Fear/drug effects/physiology, Receptors, Vasopressin/agonists/metabolism, Endocrinology, Action Potentials/drug effects/physiology, Intracellular Signaling Peptides and Proteins/ metabolism/pharmacology, nervous system, Neuron, Neuroscience, 030217 neurology & neurosurgery, Stress, Psychological
Abstract

The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx) are thought to promote arousal through the excitatory action they exert on the multiple areas to which they project within the CNS. We show here that the hcrt/orx peptides can also exert a strong action on the amygdala, a structure known for its implication in emotional aspects of behavior. Indeed, the hcrt/orx peptides, applied in acute rat brain slices, excite a specific class of "low threshold burst" neurons in the central medial (CeM) nucleus which is considered as a major output of the amygdala. These excitatory effects are postsynaptic, mediated by Hcrt2/OX2 receptors and result from the closure of a potassium conductance. They occur on a class of neurons that are also excited by vasopressin acting through V1a receptors. These results suggest that the hcrt/orx system can act through the amygdala to augment arousal and evoke the autonomic and behavioral responses associated with fear, stress or emotion.

Published
2006

9. Structure and functions of the novel hypothalamic RFamide neuropeptides R-RFa and 26RFa in vertebrates

Author

Chartrel, Nicolas, BRUZZONE, FEDERICA, Leprince, Jérôme, Tollemer, Hélène, Anouar, Youssef, Do-Régo, Jean, Ségalas-Milazzo, Isabelle, Guilhaudis, Laure, Cosette, Pascal, Jouenne, Thierry, Simonnet, Guy, VALLARINO, MAURO, Beauvillain, Jean, Costentin, Jean, Vaudry, Hubert, Do-Régo, Jean-Claude, Beauvillain, Jean-Claude, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Equipe de Chimie Organique et Biologie Structurale (ECOBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU), Polymères Biopolymères Surfaces (PBS), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Polymères, biopolymères, membranes (PBM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UMR 5287, Homéostasie-Allostasie-Pathologie-Réhabilitation, Centre National de la Recherche Scientifique (CNRS), Neuropsycho-pharmacologie expérimentale, Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
Central Nervous System, Receptors, Neuropeptide, Amphibian, Ranidae, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Central nervous system, Hypothalamus, Neuropeptide, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, Biochemistry, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, biology.animal, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Humans, MESH: Central Nervous System, MESH: Animals, Receptor, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, MESH: Humans, biology, MESH: Ranidae, MESH: Receptors, Neuropeptide, Neuropeptides, Protein primary structure, Vertebrate, MESH: Hypothalamus, Cell biology, medicine.anatomical_structure, chemistry, MESH: Oligopeptides, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Oligopeptides, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; A number of RFamide peptides have been characterized in invertebrate species and these peptides have been found to exert a broad spectrum of biological activities. In contrast, in vertebrates, our knowledge on RFamide peptides is far more limited and only a few members of the RFamide peptide family have been identified in various vertebrate classes during the last years. The present review focuses on two novel RFamide peptides, Rana RFamide (R-RFa) and 26RFa, that have been recently isolated from the amphibian brain. R-RFa shares the C-terminal LPLRFamide motif with other RFamide peptides previously identified in mammals, birds and fish. The distribution of R-RFa in the frog brain exhibits strong similarities with those of other LPLRFamide peptides, notably in the periventricular region of the hypothalamus. There is also evidence that the physiological functions of R-RFa and other LPLRFamide peptides have been conserved from fish to mammals; in particular, all these peptides appear to be involved in the control of pituitary hormone secretion. 26RFa does not exhibit any significant structural identity with other RFamide peptides and this peptide is the only member of the family that possesses an FRFamide motif at its C-terminus. The strong conservation of the primary structure of 26RFa from amphibians to mammals suggests that this RFamide peptide is involved in important biological functions in vertebrates. As for several other RFamide peptides, 26RFa-containing neurons are present in the hypothalamus, notably in two nuclei involved in the control of feeding behavior. Indeed, 26RFa is a potent stimulator of appetite in mammals. Concurrently, recent data suggest that 26RFa exerts various neuroendocrine regulatory activities at the pituitary and adrenal level.

Published
2006

10. RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia

Author

Emilie Laboureyras, Frédéric Simonin, Brigitte L. Kieffer, Jean-Paul Laulin, Marc Parmentier, Audrey Matifas, Jean-Jacques Bourguignon, Catherine Mollereau, David MacTavish, Guy Simonnet, Jack H. Jhamandas, Martine Schmitt, Patrick Laurent, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, and Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)

Subjects
Receptors, Neuropeptide, Neuropeptide FF receptor, Adamantane, Blood Pressure, Pharmacology, Ligands, MESH: Analgesics, Opioid, 0302 clinical medicine, MESH: Dipeptides, Heart Rate, Drug tolerance, Chlorocebus aethiops, MESH: Ligands, MESH: Animals, Neuropeptide FF, MESH: Heart Rate, Receptor, 0303 health sciences, Multidisciplinary, Molecular Structure, Chemistry, MESH: Receptors, Neuropeptide, Chronic pain, Sciences du Vivant [q-bio]/Biotechnologies, Dipeptides, Drug Tolerance, MESH: Adamantane, MESH: Blood Pressure, Biological Sciences, MESH: Amides, 3. Good health, Analgesics, Opioid, MESH: COS Cells, Hyperalgesia, COS Cells, MESH: Heroin, medicine.symptom, medicine.drug, MESH: Rats, MESH: Drug Tolerance, MESH: Molecular Structure, 03 medical and health sciences, medicine, Animals, Humans, 030304 developmental biology, MESH: Humans, Antagonist, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Amides, MESH: Hyperalgesia, MESH: Cercopithecus aethiops, Rats, Heroin, Opioid, 030217 neurology & neurosurgery
Abstract

International audience; Neuropeptide FF (NPFF) has been proposed to play a role in pain modulation, opioid tolerance, and several other physiological processes. However, pharmacological agents that would help define physiological roles for this peptide are still missing. Here we report the discovery of a potent and selective NPFF receptor antagonist, RF9, that can be administered systemically. This compound does not show any effects by itself but can block efficiently the increase in blood pressure and heart rate evoked by NPFF. When chronically coinjected with heroin, RF9 completely blocks the delayed and long-lasting paradoxical opioid-induced hyperalgesia and prevents the development of associated tolerance. Our data indicate that NPFF receptors are part of a bona fide antiopioid system and that selective antagonists of these receptors could represent useful therapeutic agents for improving the efficacy of opioids in chronic pain treatment.

Published
2006

11. Evidence for the presence of motilin, ghrelin, and the motilin and ghrelin receptor in neurons of the myenteric plexus

Author

Inge Depoortere, Michele Zandecki, Ming Tang, Theo L. Peeters, Catherine Tomasetto, Luo Xu, Jean-Pierre Timmermans, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Receptors, Neuropeptide, Physiology, Peptide Hormones, Motilin receptor, Clinical Biochemistry, Growth hormone secretagogue receptor, MESH: Neurons, MESH: Receptors, G-Protein-Coupled, Biochemistry, Receptors, G-Protein-Coupled, 0302 clinical medicine, Endocrinology, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Blotting, Southern, MESH: Animals, Receptors, Ghrelin, Receptor, Myenteric plexus, Neurons, MESH: Choline O-Acetyltransferase, Reverse Transcriptase Polymerase Chain Reaction, MESH: Receptors, Neuropeptide, MESH: Motilin, digestive, oral, and skin physiology, Immunohistochemistry, Choline acetyltransferase, Ghrelin, Blotting, Southern, Female, 030211 gastroenterology & hepatology, MESH: Nitric Oxide Synthase, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, Guinea Pigs, Myenteric Plexus, Biology, Choline O-Acetyltransferase, Receptors, Gastrointestinal Hormone, Motilin, MESH: Guinea Pigs, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, medicine, Animals, RNA, Messenger, MESH: Myenteric Plexus, MESH: RNA, Messenger, MESH: Receptors, Gastrointestinal Hormone, MESH: Immunohistochemistry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Male, nervous system, MESH: Peptide Hormones, Enteric nervous system, Nitric Oxide Synthase, MESH: Female, 030217 neurology & neurosurgery
Abstract

Motilin, a 22-amino acid gastrointestinal peptide, and ghrelin, the natural ligand of the growth hormone secretagogue receptor, form a new group of structurally related peptides. Several lines of evidence suggest that motilin and ghrelin are involved in the control of gastrointestinal motility by the activation of receptors on enteric neurons. The aim of this study was to look for the existence of motilin, ghrelin, and their respective receptors in the myenteric plexus of the guinea pig. We used longitudinal muscle/myenteric plexus (LMMP) preparations and cultures of myenteric neurons of the guinea pig ileum, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR). Most of the motilin-immunoreactive (IR; 72.8%) and motilin receptor-IR (68.9%) neurons were also positive for neuronal nitric oxide synthase (nNOS), 72.8% and 68.9%, few for choline acetyl transferase (ChAT), 11.4% and 11.9%, respectively. In contrast, ghrelin was mainly colocalized with ChAT (72.2%), and only 3.6% of ghrelin-positive cells showed nNOS-IR in the LMMP. Neither motilin nor the motilin receptor or ghrelin colocalized with calbindin. RT-PCR studies revealed motilin, ghrelin, and ghrelin receptor mRNA transcripts in LMMP preparations and in cultured myenteric neurons. In conclusion, this study, for the first time, provides direct evidence for the existence of motilin and ghrelin in myenteric neurons and suggests that both peptides may play a role in the activation of the enteric nervous system and hence in the regulation of gastrointestinal motility.

Published
2005

12. Nonpeptide antagonists of neuropeptide receptors: tools for research and therapy

Author

Mounia Azzi, William Rostène, Catalina Betancur, Betancur, Catalina, Imagerie cellulaire des neurorécepteurs et physiopathologie neuroendocrinienne, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and C.B. is a recipient of a post-doctoral fellowship from INSERM (Institut National de la Santé et de la Recherche Medicale), France.

Subjects
Receptors, Neuropeptide, neuropeptide Y, Stereochemistry, Molecular Sequence Data, neurotensin, Neuropeptide, Peptide, MESH: Amino Acid Sequence, Pharmacology, Biology, Toxicology, nonpeptide antagonist, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, corticotropin releasing factor, MESH: Receptors, Tachykinin, Animals, Humans, MESH: Animals, Amino Acid Sequence, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Receptor, peptide receptor, Receptors, Tachykinin, Cholecystokinin, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, MESH: Humans, MESH: Molecular Sequence Data, MESH: Receptors, Neuropeptide, tachykinin, angiotensin, Neuropeptide Y receptor, 3. Good health, cholecystokinin, Orally active, chemistry, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Tachykinin receptor, 030217 neurology & neurosurgery, Neurotensin
Abstract

International audience; The recent development of selective and highly potent nonpeptide antagonists for peptide receptors has constituted a major breakthrough in the field of neuropeptide research. Following the discovery of the first nonpeptide antagonists for peptide receptors ten years ago, numerous other antagonists have been developed for most neuropeptide families. These new, metabolically stable compounds, orally active and capable of crossing the blood-brain barrier, offer clear advantages over the previously available peptide antagonists. Nonpeptide antagonists have provided valuable tools to investigate peptide receptors at the molecular, pharmacological and anatomical levels, and have considerably advanced our understanding of the pathophysiological roles of peptides in the CNS and periphery. Evidence from animal and clinical studies suggests that nonpeptide antagonists binding to peptide receptors could be useful for the treatment of disease states associated with high levels of neuropeptides. In this article Catalina Betancur, Mounia Azzi and William Rostène will address the recent developments in nonpeptide antagonists for neuropeptide receptors, with a particular focus on their CNS actions.

Published
1997

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