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: Luigi Brunetti, Claudio Ferrante, Giustino Orlando, Lucia Recinella, Sheila Leone, Annalisa Chiavaroli, Chiara Di Nisio, Rugia Shohreh, Fabio Manippa, Adriana Ricciuti, Adriano Mollica, Michele Vacca
• Journal: Peptides (Peptides) Vol. 48 Pg. 83-8 (Oct 2013) ISSN: 1873-5169 [Electronic] United States
• PMID: 23916912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Agouti-Related Protein
• HCRT protein, human
• Intracellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Neuropeptide Y
• Neuropeptides
• Oligopeptides
• Orexins
• cocaine- and amphetamine-regulated transcript protein
• Serotonin
• endomorphin 2
• Naltrexone
• Pro-Opiomelanocortin
• beta-funaltrexamine
• Corticotropin-Releasing Hormone
• Dopamine
• Norepinephrine

Topics

• Agouti-Related Protein
• Animals
• Arcuate Nucleus of Hypothalamus (metabolism, physiology)
• Corticotropin-Releasing Hormone (genetics, metabolism)
• Dopamine (metabolism)
• Feeding Behavior (drug effects)
• Gene Expression Regulation (drug effects)
• Humans
• Hypothalamus (metabolism)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Naltrexone (administration & dosage, analogs & derivatives)
• Nerve Tissue Proteins (metabolism)
• Neuropeptide Y (metabolism)
• Neuropeptides (metabolism)
• Norepinephrine (metabolism)
• Oligopeptides (administration & dosage, metabolism)
• Orexins
• Pro-Opiomelanocortin (metabolism)
• Rats
• Serotonin (metabolism)