Artículo
Melanocortin 4 receptor constitutive activity inhibits L-type voltage-gated calcium channels in neurons
Agosti, Francina
; Cordisco Gonzalez, Santiago; Martínez Damonte, Valentina
; Tolosa, María José
; Di Siervi, Nicolás; Schioth, H. B.; Davio, Carlos Alberto
; Perello, Mario
; Raingo, Jesica
Fecha de publicación:
03/2017
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Neuroscience
ISSN:
0306-4522
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (CaV2.2) are inhibited by MC4R agonist-dependent activation, while the CaV subtypes that carry L- and P/Q-type current are not. Here, we tested the hypothesis that MC4R constitutive activity can affect CaV, with focus on the channel subtypes that can control transcriptional activity coupled to depolarization (L-type, CaV1.2/1.3) and neurotransmitter release (N- and P/Q-type, CaV2.2 and CaV2.1). We found that MC4R constitutive activity inhibits specifically CaV1.2/1.3 and CaV2.1 subtypes of CaV. We also explored the signaling pathways mediating this inhibition, and thus propose that agonist-dependent and basal MC4R activation modes signal differentially through Gs and Gi/o pathways to impact on different CaV subtypes. In addition, we found that chronic incubation with MC4R endogenous inverse agonist, agouti and agouti-related peptide (AgRP), occludes CaV inhibition in a cell line and in amygdaloid complex cultured neurons as well. Thus, we define new mechanisms of control of the main mediators of depolarization-induced calcium entry into neurons by a GPCR that displays constitutive activity.
Palabras clave:
Amygdala
,
Calcium Channels
,
Electrophysiology
,
G Protein
,
Melanocortin Receptor
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IMBICE)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Citación
Agosti, Francina; Cordisco Gonzalez, Santiago; Martínez Damonte, Valentina; Tolosa, María José; Di Siervi, Nicolás; et al.; Melanocortin 4 receptor constitutive activity inhibits L-type voltage-gated calcium channels in neurons; Pergamon-Elsevier Science Ltd; Neuroscience; 346; 3-2017; 102-112
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