Characterization of dopamine D2 receptor coupling to G proteins in postmortem brain of subjects with schizophrenia
dc.contributor.author | Egusquiza, Iker | |
dc.contributor.author | Munarriz Cuezva, Eva | |
dc.contributor.author | Segarra Echevarria, Rafael | |
dc.contributor.author | González Maeso, Javier | |
dc.contributor.author | Callado Hernando, Luis Felipe | |
dc.contributor.author | Meana Martínez, José Javier | |
dc.contributor.author | Díez Alarcia, Rebeca | |
dc.date.accessioned | 2022-01-07T11:01:56Z | |
dc.date.available | 2022-01-07T11:01:56Z | |
dc.date.issued | 2021-08 | |
dc.identifier.citation | Pharmacological Reports 73(4) :1136-1146 (2021) Número especial | es_ES |
dc.identifier.issn | 1734-1140 | |
dc.identifier.issn | 2299-5684 | |
dc.identifier.issn | 10.1007/s43440-021-00305-4 | |
dc.identifier.uri | http://hdl.handle.net/10810/54834 | |
dc.description.abstract | Background: Alterations of dopamine D-1 (D1R) and D-2 receptor (D2R) are proposed in schizophrenia but brain neuroimaging and postmortem studies have shown controversial results in relation to D1R and D2R density. Besides, scarce information on the functionality of brain D1R and D2R is available. The present study characterized G-protein activation by D1R and D2R agonists in postmortem human brain. Furthermore, D2R functional status was compared between schizophrenia and control subjects. Methods: G-protein receptor coupling was assessed in control caudate nucleus and frontal cortex by [S-35]GTP gamma S-binding stimulation induced by increasing concentrations (10(-10)-10(-3) M) of dopamine, and the selective dopaminergic agonists SKF38393 (D1R) and NPA (D2R). Concentration-response curves to NPA stimulation of [S-35]GTP gamma S binding were analyzed in antipsychotic-free (n = 10) and antipsychotic-treated (n = 7) schizophrenia subjects and matched controls (n = 17). Results: In caudate, [S-35]GTP gamma S-binding responses to agonists were compatible with the existence of functional D2R. In contrast, stimulations in cortex showed responses that did not correspond to D1R or D2R. [S-35]GTP gamma S-binding activation by NPA in caudate displayed biphasic curves with similar profile in schizophrenia (EC50H = 7.94 nM; EC50L = 7.08 mu M) and control (EC50H = 7.24 nM; EC50L = 15.14 mu M) subjects. The presence or absence of antipsychotic medication did not influence the pharmacological parameters. Conclusions: Feasibility of functional evaluation of dopamine receptors in postmortem human brain by conventional [S-35]GTP gamma S-binding assays appears to be restricted to signalling through inhibitory G(i/o) proteins. These findings provide functional information about brain D2R status in subjects with schizophrenia and do not support the existence of D2R supersensitive in this mental disorder. | es_ES |
dc.description.sponsorship | This work was supported by the Spanish State Research Agency and EDR Funds (SAF-2017-88126-R to JJM;PID2019-106404RB-100 to LFC), the Basque Government (IT1211/19 to JJM ; ELKARTEK Programme KK-2019/00049 to RD-A), and the National Institutes of Health (R01MH084894 & NIH-R01MH111940 to JG-M). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/SAF-2017-88126-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-106404RB-100 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | D-2 receptors | es_ES |
dc.subject | schizophrenia | es_ES |
dc.subject | G protein | es_ES |
dc.subject | Human brain | es_ES |
dc.subject | [S-35]GTP gamma S | es_ES |
dc.subject | dopamine | es_ES |
dc.subject | gamma-S | es_ES |
dc.subject | binding | es_ES |
dc.subject | mediated activation | es_ES |
dc.subject | rat striatum | es_ES |
dc.subject | agonist | es_ES |
dc.subject | assay | es_ES |
dc.subject | autoradiography | es_ES |
dc.subject | pharmacology | es_ES |
dc.subject | haloperidol | es_ES |
dc.subject | antagonist | es_ES |
dc.title | Characterization of dopamine D2 receptor coupling to G proteins in postmortem brain of subjects with schizophrenia | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://link.springer.com/article/10.1007%2Fs43440-021-00305-4 | es_ES |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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