p38 MAPK and beta-arrestin 2 mediate functional interactions between endogenous micro-opioid and alpha2A-adrenergic receptors in neurons.
J Biol Chem
; 284(10): 6270-81, 2009 Mar 06.
Article
en En
| MEDLINE
| ID: mdl-19126537
ABSTRACT
Formation of receptor complexes between micro-opioid and alpha2A-adrenergic receptors has been demonstrated in transfected cells. The functional significance and underlying mechanisms of such receptor interactions remain to be determined in neuronal systems. We examined functional interactions between endogenous micro and alpha2A receptors in mouse dorsal root ganglion neurons. Acute application of the micro agonist [D-Ala2,N-MePhe4, Gly-ol5]enkephalin (DAMGO) or the alpha2 agonist clonidine inhibited voltage-gated Ca2+ currents in these neurons. Prolonged treatment with either DAMGO or clonidine induced a mutual cross-desensitization between micro and alpha2A receptor-mediated current inhibition. The cross-desensitization was closely associated with simultaneous internalization of micro and alpha2A receptors. Morphine, a mu agonist triggering little mu receptor endocytosis, induced neither cross-desensitization nor internalization of alpha2A receptors. Furthermore, inhibition of p38 MAPK prevented the cross-desensitization as well as cointernalization of micro and alpha2A receptors. Changes in receptor trafficking profiles suggested that p38 MAPK activity was required for initiating micro receptor internalization and maintaining possible micro-alpha2A association during their cointernalization. Finally, the micro-alpha2A cross-desensitization was absent in dorsal root ganglion neurons lacking beta-arrestin 2. These findings demonstrated p38 MAPK- and beta-arrestin 2-dependent cross-regulation between neuronal micro and alpha2A receptors. By promoting receptor cross-desensitization and cointernalization, such functional interactions may serve as negative feedback mechanisms triggered by prolonged agonist exposure to modulate the signaling of functionally related G protein-coupled receptors.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores Adrenérgicos alfa 2
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Receptores Opioides mu
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Arrestinas
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Proteínas Quinasas p38 Activadas por Mitógenos
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Ganglios Espinales
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos