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Rep"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Alterations of dopamine D<jats:sub>1<\/jats:sub> (D1R) and D<jats:sub>2<\/jats:sub> receptor (D2R) are proposed in schizophrenia but brain neuroimaging and <jats:italic>postmortem<\/jats:italic> 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 <jats:italic>postmortem<\/jats:italic> human brain. Furthermore, D2R functional status was compared between schizophrenia and control subjects.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>G-protein receptor coupling was assessed in control caudate nucleus and frontal cortex by [<jats:sup>35<\/jats:sup>S]GTP\u03b3S-binding stimulation induced by increasing concentrations (10<jats:sup>\u201310<\/jats:sup>\u201310<jats:sup>\u20133<\/jats:sup>\u00a0M) of dopamine, and the selective dopaminergic agonists SKF38393 (D1R) and NPA (D2R). Concentration\u2013response curves to NPA stimulation of [<jats:sup>35<\/jats:sup>S]GTP\u03b3S binding were analyzed in antipsychotic-free (<jats:italic>n<\/jats:italic>\u2009=\u200910) and antipsychotic-treated (<jats:italic>n<\/jats:italic>\u2009=\u20097) schizophrenia subjects and matched controls (<jats:italic>n<\/jats:italic>\u2009=\u200917).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In caudate, [<jats:sup>35<\/jats:sup>S]GTP\u03b3S-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. [<jats:sup>35<\/jats:sup>S]GTP\u03b3S-binding activation by NPA in caudate displayed biphasic curves with similar profile in schizophrenia (EC<jats:sub>50H<\/jats:sub>\u2009=\u20097.94\u00a0nM; EC<jats:sub>50L<\/jats:sub>\u2009=\u20097.08\u00a0\u03bcM) and control (EC<jats:sub>50H<\/jats:sub>\u2009=\u20097.24\u00a0nM; EC<jats:sub>50L<\/jats:sub>\u2009=\u200915.14\u00a0\u03bcM) subjects. The presence or absence of antipsychotic medication did not influence the pharmacological parameters.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Feasibility of functional evaluation of dopamine receptors in <jats:italic>postmortem<\/jats:italic> human brain by conventional [<jats:sup>35<\/jats:sup>S]GTP\u03b3S-binding assays appears to be restricted to signalling through inhibitory G<jats:sub>i\/o<\/jats:sub> 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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s43440-021-00305-4","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T09:03:20Z","timestamp":1625130200000},"page":"1136-1146","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of dopamine D2 receptor coupling to G proteins in postmortem brain of subjects with schizophrenia"],"prefix":"10.1007","volume":"73","author":[{"given":"Iker","family":"Egusquiza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-3642","authenticated-orcid":false,"given":"Eva","family":"Munarriz-Cuezva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-8151","authenticated-orcid":false,"given":"Rafael","family":"Segarra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Gonz\u00e1lez-Maeso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-012X","authenticated-orcid":false,"given":"Luis F.","family":"Callado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7913-6714","authenticated-orcid":false,"given":"J. 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