Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/199586
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | HINT1 protein: A new therapeutic target to enhance opioid antinociception and block mechanical allodynia |
Autor: | Garzón, Javier CSIC ORCID ; Herrero-Labrador, Raquel CSIC ORCID; Rodríguez-Muñoz, María; Shah, Rachit; Vicente-Sánchez, Ana CSIC; Wagner, Carston R.; Sánchez-Blázquez, Pilar CSIC ORCID | Palabras clave: | Histidine triad nucleotide binding protein 1 Mu-opioid receptor Glutamate N-methyl-d-aspartate receptor Guanosine-5′-tryptamine carbamate PKCγ Antinociception Receptor desensitization |
Fecha de publicación: | feb-2015 | Editor: | Elsevier BV | Citación: | Neuropharmacology 89: 412-423 (2015) | Resumen: | In the nervous system, the glutamate N-methyl-d-aspartate receptor (NMDAR) restricts the activity of the mu-opioid receptor (MOR). Both receptors are present in midbrain periaqueductal grey (PAG) neurons, an area that plays a central role in the supraspinal antinociceptive effects of opioids. The cross-talk that occurs between these receptors is sustained by the MOR-associated histidine triad nucleotide binding protein 1 (HINT1), which displays nucleoside phosphoramidase and acyl-AMP hydrolase activity. Here we report that the inhibitor of HINT1 enzymatic activity guanosine-5′-tryptamine carbamate (TpGc) significantly enhanced morphine antinociception while preventing the development of tolerance. At the molecular level, TpGc reduced the capacity of MORs to recruit NMDAR activity to negatively regulate opioid signaling. In mice suffering from chronic constriction injury concurrent with increased NMDAR activity, a single intracerebroventricular administration of TpGc attenuated NMDAR function and alleviated mechanical allodynia for several days. These data suggest a potential therapeutic role for HINT1 inhibitors in the clinical management of acute and neuropathic pain. | Versión del editor: | http://dx.doi.org/10.1016/j.neuropharm.2014.10.022 | URI: | http://hdl.handle.net/10261/199586 | DOI: | 10.1016/j.neuropharm.2014.10.022 | ISSN: | 0028-3908 | E-ISSN: | 1873-7064 |
Aparece en las colecciones: | (IC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
35
checked on 01-may-2024
WEB OF SCIENCETM
Citations
32
checked on 16-feb-2024
Page view(s)
140
checked on 02-may-2024
Download(s)
23
checked on 02-may-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.