Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors.
Mol Neurobiol
; 56(2): 1196-1210, 2019 Feb.
Article
en En
| MEDLINE
| ID: mdl-29876881
ABSTRACT
Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ1R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ1R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ1R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781. Results were similar in G protein-dependent (cAMP accumulation and calcium release) and in partly dependent or independent (ERK1/2 phosphorylation and label-free) assays. We provide solid evidence for direct interaction between receptors and the functional consequences, as well as a reliable structural model of the macromolecular σ1R-GHS-R1a complex, which arises as a key piece in the puzzle of the events linking cocaine consumption and appetitive/consummatory behaviors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Ácido Oleanólico
/
Saponinas
/
Receptores sigma
/
Cocaína
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Inhibidores de Captación de Dopamina
/
Cuerpo Estriado
/
Ghrelina
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
España