title: Orexigenic effects of endomorphin-2 (EM-2) related to decreased CRH gene expression and increased dopamine and norepinephrine activity in the hypothalamus.
abstract: Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are opioid peptides which are selective partial agonists of μ-opioid receptor. We studied the effects of EM-2 injected into the arcuate nucleus (ARC) of the hypothalamus on feeding behavior and gene expression of orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART), corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC)] peptides in male Wistar rats fed a standard laboratory diet. Furthermore, we evaluated the effects of EM-2 on dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) steady state concentrations, in the hypothalamus. 64 rats (16 for each group of treatment) were injected into the ARC, at 9.00 am, with either vehicle or EM-2 (0.50-0.75 μmol/kg) or EM-2 (0.50 μmol/kg) plus β-funaltrexamine (0.20 μmol/kg). Food intake was recorded through 24h following injection, and hypothalamic DA, NE, 5-HT levels and neuropeptide gene expression were evaluated 24h after EM-2 administration. Compared to vehicle, EM-2 significantly increased food intake, throughout 24h post-injection. Furthermore, EM-2 treatment led to a significant increase of DA and NE concentrations and a decrease of CRH mRNA levels. On the other hand, β-funaltrexamine administration reverted both feeding stimulatory and neuromodulatory effects induced by EM-2. We can conclude that the orexigenic effect of μ-opioid receptor activation by EM-2 could be related to both inhibition of CRH and stimulation of dopamine and norepinephrine levels, in the hypothalamus.
authors.affiliation: Department of Pharmacy, "G. d'Annunzio" University, via dei Vestini 31, 66013 Chieti, Italy. Electronic address: brunetti@unich.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferrante
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.forename: Lucia
authors.initials: L
authors.lastname: Recinella
authors.forename: Sheila
authors.initials: S
authors.lastname: Leone
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiavaroli
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Nisio
authors.forename: Rugia
authors.initials: R
authors.lastname: Shohreh
authors.forename: Fabio
authors.initials: F
authors.lastname: Manippa
authors.forename: Adriana
authors.initials: A
authors.lastname: Ricciuti
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
mesh_terms: D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism; D000068797:Orexins; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D009842:Oligopeptides; D000068797:Orexins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D012701:Serotonin; C105294:endomorphin 2; D009271:Naltrexone; D011333:Pro-Opiomelanocortin; C024524:beta-funaltrexamine; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine; D009638:Norepinephrine
keywords: 5-HT; ARC; AgRP; CART; CRH; Corticotrophin-releasing hormone; DA; Dopamine; EM-2; Endomorphin-2; Feeding; Hypothalamus; NE; NPY; Norepinephrine; POMC; PVN; Real-time RT PCR; agouti-related peptide; arcuate nucleus; cocaine and amphetamine-regulated transcript; corticotrophin releasing hormone; dopamine; endomorphin-2; neuropeptide Y; norepinephrine; paraventricular nucleus; pro-opiomelanocortin; real-time reverse transcription polymerase chain reaction; serotonin