Previous studies have demonstrated an effect of corticotropin-releasing factor 2 receptor (CRF2R) agonists in the maintenance of skeletal muscle mass. The aim of this study was to evaluate the effects of a CRF2R agonist in preserving skeletal muscle in a mouse cachexia model. Implantation of a fast-growing tumor to mice (Lewis lung carcinoma) resulted in a clear cachectic state characterized by a profound muscle wasting. We found that administration of a CRF2R agonist (PG-873637) at 100 microg/kg/day by means of osmotic minipumps to tumor-bearing mice resulted in beneficial effects on muscle weight loss. Thus, muscle loss was partially reversed by the CRF2R agonist at different stages of tumor growth (at day 14 after tumor inoculation: 12% in tibialis posterior; 9% in gastrocnemius; and 48% in soleus). Moreover, the CRF2R agonist significantly reduced both the number of metastases and their mass (at day 19 after tumor inoculation: 66% and 61%, respectively). These data suggest a potentially beneficial effect of the CRF2R agonist in preserving skeletal muscle during cancer cachexia and open a line of research for the development of new therapeutic approaches for the treatment of muscle wasting associated with cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/mus.20899 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural and Functional Insights into CRF Peptides and Their Receptors.
Biology (Basel)
February 2024
Department of Pharmacology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.
Corticotropin-releasing factor or hormone (CRF or CRH) and the urocortins regulate a plethora of physiological functions and are involved in many pathophysiological processes. CRF and urocortins belong to the family of CRF peptides (CRF family), which includes sauvagine, urotensin, and many synthetic peptide and non-peptide CRF analogs. Several of the CRF analogs have shown considerable therapeutic potential in the treatment of various diseases.
View Article and Find Full Text PDFDifferential effect of amphetamine over the corticotropin-releasing factor CRF receptor, the orexin OX receptor and the CRF-OX heteroreceptor complex.
Neuropharmacology
July 2019
Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain; Molecular Neurobiology Laboratory, Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Spain. Electronic address:
Stress is one of the factors underlying drug seeking behavior that often goes in parallel with loss of appetite. We here demonstrate that orexin 1 receptors (OXR) may form complexes with the corticotropin releasing factor CRF receptor. Two specific features of the heteromer were a cross-antagonism and a blockade by CRF of OXR signaling.
View Article and Find Full Text PDFExtended Amygdala to Ventral Tegmental Area Corticotropin-Releasing Factor Circuit Controls Binge Ethanol Intake.
Biol Psychiatry
June 2017
Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:
Background: Corticotropin-releasing factor (CRF) signaling at the CRF receptor (CRFR) in the ventral tegmental area (VTA) can modulate ethanol consumption in rodents. However, the effects of binge-like ethanol drinking on this system have not been thoroughly characterized, and little is known about the role of CRFR or the CRF neurocircuitry involved.
Methods: The effects of binge-like ethanol consumption on the VTA CRF system were assessed following drinking-in-the-dark procedures.
Corticotropin-releasing factor type-2 receptor and corticotropin-releasing factor-binding protein coexist in rat ventral tegmental area nerve terminals originated in the lateral hypothalamic area.
Eur J Neurosci
January 2016
Department of Cellular and Molecular Biology, Millenium Science Nucleus in Stress and Addiction, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, 8331150, Chile.
There is significant functional evidence showing that corticotropin-releasing factor type-2 receptor (CRF2R) and corticotropin-releasing factor-binding protein (CRF-BP) regulate glutamatergic synapses onto ventral tegmental area (VTA) dopaminergic neurons. It has been shown that CRF requires CRF-BP to potentiate N-methyl-D-aspartate receptors in dopaminergic neurons through CRF2R, and that increases glutamate release in cocaine-treated rats through the activation of CRF2R only by agonists with high affinity to CRF-BP. Furthermore, this CRF-mediated increase in VTA glutamate is responsible for stress-induced relapse to cocaine-seeking behaviour.
View Article and Find Full Text PDFNeuroprotection afforded by adenosine A2A receptor blockade is modulated by corticotrophin-releasing factor (CRF) in glutamate injured cortical neurons.
J Neurochem
December 2012
Institute of Pharmacology and Neurosciences, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
In situations of hypoxia, glutamate excitotoxicity induces neuronal death. The release of extracellular adenosine is also triggered and is accompanied by an increase of the stress mediator, corticotrophin-releasing factor (CRF). Adenosine A(2A) receptors contribute to glutamate excitoxicity and their blockade is effective in stress-induced neuronal deficits, but the involvement of CRF on this effect was never explored.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!