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http://hdl.handle.net/2445/122586
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DC Field | Value | Language |
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dc.contributor.author | Moreno Guillén, Estefanía | - |
dc.contributor.author | Moreno-Delgado, David | - |
dc.contributor.author | Navarro Brugal, Gemma | - |
dc.contributor.author | Hoffmann, Hanne | - |
dc.contributor.author | Fuentes, Silvia | - |
dc.contributor.author | Rosell-Vilar, Santi | - |
dc.contributor.author | Gasperini, Paola | - |
dc.contributor.author | Rodríguez Ruiz, Mar | - |
dc.contributor.author | Medrano Moya, Mireia | - |
dc.contributor.author | Mallol Montero, Josefa | - |
dc.contributor.author | Cortés Tejedor, Antonio | - |
dc.contributor.author | Casadó, Vicent | - |
dc.contributor.author | Lluís i Biset, Carme | - |
dc.contributor.author | Ferré, Sergi | - |
dc.contributor.author | Ortiz, Jordi | - |
dc.contributor.author | Canela Campos, Enric I. | - |
dc.contributor.author | McCormick, Peter J. | - |
dc.date.accessioned | 2018-05-25T17:39:32Z | - |
dc.date.available | 2018-05-25T17:39:32Z | - |
dc.date.issued | 2014-03-05 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | http://hdl.handle.net/2445/122586 | - |
dc.description.abstract | The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | The Society for Neuroscience | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1523/JNEUROSCI.4147-13.2014 | - |
dc.relation.ispartof | Journal of Neuroscience, 2014, vol. 34, num. 10, p. 3545-3558 | - |
dc.relation.uri | https://doi.org/10.1523/JNEUROSCI.4147-13.2014 | - |
dc.rights | cc-by-nc-sa (c) Moreno Guillén, Estefanía et al., 2014 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/es | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Cocaïna | - |
dc.subject.classification | Receptors cel·lulars | - |
dc.subject.classification | Dopamina | - |
dc.subject.other | Cocaine | - |
dc.subject.other | Cell receptors | - |
dc.subject.other | Dopamine | - |
dc.title | Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: σ1-D1-H3 receptor complexes as key targets for reducing cocaine's effects | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 634916 | - |
dc.date.updated | 2018-05-25T17:39:33Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24599455 | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Bioquímica i Fisiologia) |
Files in This Item:
File | Description | Size | Format | |
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634916.pdf | 3.38 MB | Adobe PDF | View/Open |
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