2026-04-17T12:02:25Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1273062025-12-04T21:16:29Zcom_2072_1057col_2072_478781col_2072_478917
RECERCAT author Aguinaga Andrés, David author Medrano Moya, Mireia author Cordomí, Arnau author Jiménez-Rosés, Mireia author Angelats Canals, Edgar author Casanovas Ferrero, Mireia author Vega-Quiroga, Ignacio author Canela Campos, Enric I. (Enric Isidre), 1949- author Petrovic, Milos author Gysling, Katia author Pardo, Leonardo author Franco Fernández, Rafael author Navarro Brugal, Gemma 2019-01-15T16:00:55Z2019-06-07T05:10:09Z2018-06-072019-01-15T16:00:55Z 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. (c) Humana Press., 2018 info:eu-repo/semantics/openAccess Neuroendocrinologia Receptors cel·lulars Drogues Cocaïna Neuroendocrinology Cell receptors Drugs of abuse Cocaine Cocaine blocks effects of hunger hormone, ghrelin, via interaction with neuronal sigma-1 receptors. info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion