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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
Casanovas Ferrero, Mireia
Canela Campos, Enric I.
Franco Fernández, Rafael
Navarro Brugal, Gemma
Drugs of abuse
|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: https://doi.org/10.1007/s12035-018-1140-7|
|It is part of:||Molecular Neurobiology, 2018, vol. 200, p. 1-10|
|Appears in Collections:||Articles publicats en revistes (Bioquímica i Biomedicina Molecular)|
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