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Cocaine blocks effects of hunger hormone, ghrelin, via interaction with neuronal sigma-1 receptors.
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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.
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AGUINAGA ANDRÉS, David, MEDRANO MOYA, Mireia, CORDOMÍ, Arnau, JIMÉNEZ-ROSÉS, Mireia, ANGELATS CANALS, Edgar, CASANOVAS FERRERO, Mireia, VEGA-QUIROGA, Ignacio, CANELA CAMPOS, Enric i. (enric isidre), PETROVIC, Milos, GYSLING, Katia, PARDO, Leonardo, FRANCO FERNÁNDEZ, Rafael, NAVARRO BRUGAL, Gemma. Cocaine blocks effects of hunger hormone, ghrelin, via interaction with neuronal sigma-1 receptors.. _Molecular Neurobiology_. 2018. Vol. 200, núm. 1-10. [consulta: 10 de abril de 2026]. ISSN: 0893-7648. [Disponible a: https://hdl.handle.net/2445/127306]