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Title: Cocaine blocks effects of hunger hormone, ghrelin, via interaction with neuronal sigma-1 receptors.
Author: Aguinaga Andrés, David
Medrano Moya, Mireia
Cordomí, Arnau
Jiménez-Rosés, Mireia
Angelats, Edgar
Casanovas Ferrero, Mireia
Vega-Quiroga, Ignacio
Canela Campos, Enric I.
Petrovic, Milos
Gysling, Katia
Pardo, Leonardo
Franco Fernández, Rafael
Navarro Brugal, Gemma
Keywords: Neuroendocrinologia
Receptors cel·lulars
Cell receptors
Drugs of abuse
Issue Date: 7-Jun-2018
Publisher: Humana Press.
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.
Note: Versió postprint del document publicat a:
It is part of: Molecular Neurobiology, 2018, vol. 200, p. 1-10
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ISSN: 0893-7648
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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