dc.contributor.author | García Bea, Aintzane | |
dc.contributor.author | Miranda Azpiazu, Patricia | |
dc.contributor.author | Muguruza Millán, Carolina | |
dc.contributor.author | Marmolejo Martínez-Arteseroa, Sara | |
dc.contributor.author | Díez Alarcia, Rebeca | |
dc.contributor.author | Gabilondo Urquijo, Ane Miren | |
dc.contributor.author | Callado Hernando, Luis Felipe | |
dc.contributor.author | Morentin Campillo, Benito | |
dc.contributor.author | González Maeso, Javier | |
dc.contributor.author | Meana Martínez, José Javier | |
dc.date.accessioned | 2020-03-05T13:39:40Z | |
dc.date.available | 2020-03-05T13:39:40Z | |
dc.date.issued | 2019-12 | |
dc.identifier.citation | European Neuropsychopharmacology 29(12) : 1453-1463 (2019) | es_ES |
dc.identifier.issn | 0924-977X | |
dc.identifier.issn | 1873-7862 | |
dc.identifier.uri | http://hdl.handle.net/10810/41959 | |
dc.description.abstract | Serotonin 5-HT2A receptors (5-HT(2A)Rs) have been implicated in schizophrenia. However, postmortem studies on 5-HT(2A)Rs expression and functionality in schizophrenia are scarce. The 5-HT2AR mRNA and immunoreactive protein expression were evaluated in postmortem tissue from dorsolateral prefrontal cortex (DLPFC) of antipsychotic-free (n = 18) and antipsychotic-treated (n = 9) subjects with schizophrenia, and matched controls (n = 27). Functional coupling of 5-HT2AR to G-proteins was tested by measuring the activation induced by the agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride ((+/-)DOI) in antibody-capture [S-35]GTP gamma S scintillation proximity assays (SPA). In antipsychotic-free schizophrenia subjects, 5-HT2AR mRNA expression and protein immunoreactivity in total homogenates was similar to controls. In contrast, in antipsychotic-treated schizophrenia subjects, lower mRNA expression (60 +/- 9% vs controls) and a trend to reduced protein immunoreactivity (86 +/- 5% vs antipsychotic-free subjects) just in membrane-enriched fractions was observed. [S-35]GTP gamma S SPA revealed a significant (similar to)6% higher stimulation of G(alpha i1)-protein by (+/-)DOI in schizophrenia, whereas activation of the canonical G(alpha q/11)-protein pathway by (+/-)DOI remained unchanged. Expression of G(alpha i1) - and G(alpha q/11)-proteins did not differ between groups. Accordingly, in rats chronically treated with clozapine, but not with haloperidol, a 30-40% reduction was observed in 5-HT2AR mRNA expression, 5-HT2AR protein immunoreactivity and [H-3]ketanserin binding in brain cortical membranes. Overall, the data suggest a supersensitive 5-HT2AR signaling through inhibitory G(alpha i1)-proteins in schizophrenia. Together with previous results, a dysfunctional pro-hallucinogenic agonist-sensitive 5-HT2AR conformation in postmortem DLPFC of subjects with schizophrenia is proposed. Atypical antipsychotic treatment would contribute to counterbalance this 5-HT2AR supersensitivity by reducing receptor expression. (C) 2019 The Author(s). Published by Elsevier B.V. | es_ES |
dc.description.sponsorship | This study was supported by US National Institutes of Health (NIH) (R01 MH084894 and R01MH111940 to JG-M), Spanish Ministry of Science, Innovation and Universities and European ERDF Funds (SAF2009-08460 and 2017-88126-R to JJM), and the Basque Government (IT-616-13 and IT-1211-19 to JJM). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-88126-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2009-08460-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | serotonin 2a receptor | es_ES |
dc.subject | schizophrenia | es_ES |
dc.subject | human brain | es_ES |
dc.subject | g protein | es_ES |
dc.subject | antipsychotics | es_ES |
dc.subject | lysergic-acid diethylamide | es_ES |
dc.subject | messenger-rna expression | es_ES |
dc.subject | 2a receptor | es_ES |
dc.subject | prefrontal cortex | es_ES |
dc.subject | binding | es_ES |
dc.subject | modulation | es_ES |
dc.subject | depression | es_ES |
dc.subject | responses | es_ES |
dc.title | Serotonin 5-HT2A receptor expression and functionality in postmortem frontal cortex of subjects with schizophrenia: Selective biased agonism via Gαi1-proteins | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | ©2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. ( http://creativecommons.org/licenses/by-nc-nd/4.0/ | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0924977X19317250?via%3Dihub | es_ES |
dc.identifier.doi | 10.1016/j.euroneuro.2019.10.013 | |
dc.departamentoes | Especialidades médico-quirúrgicas | es_ES |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
dc.departamentoeu | Medikuntza eta kirurgia espezialitateak | es_ES |