@article{ref1,
title="Regulation of platelet alpha 2A-adrenoceptors, Gi proteins and receptor kinases in major depression: effects of mirtazapine treatment",
journal="Neuropsychopharmacology",
year="2004",
author="García-Sevilla, Jesús A. and Ventayol, Pedro and Perez, Victor and Rubovszky, Grégoire and Puigdemont, Dolors and Ferrer-Alcón, Marcel and Andreoli, Antonio and Guimón, José and Álvarez, Enric",
volume="29",
number="3",
pages="580-588",
abstract="Major depression is associated with the upregulation of alpha(2A)-adrenoceptors in brain tissue and blood platelets. The homologous regulation of these receptors by G-protein-coupled receptor kinases (GRKs) might play a relevant role in the pathogenesis and treatment of depression. This study was designed to assess the status of the complex alpha(2A)-adrenoceptor/Galphai/GRK 2 in the platelets of depressed patients (n=22) before and after treatment with the antidepressant mirtazapine, an antagonist at alpha(2A)-adrenoceptors (30-45 mg/day for up to 6 months). A second series of depressed suicide attempters (n=32) were also investigated to further assess the status of platelet GRK 2 and GRK 6. Platelet alpha(2A)-adrenoceptors and Galphai protein immunoreactivities were increased in depressed patients (49 and 35%) compared with matched controls. In contrast, GRK 2 content was decreased in the two series of depressed patients (27 and 28%). GRK 6 (a GRK with different properties) was found unchanged. In drug-free depressed patients, the severity of depression (behavioral ratings with two different instruments) correlated inversely with the content of platelet GRK 2 (r=-0.46, n=22, p=0.032, and r=-0.55, n=22, p=0.009). After 4-24 weeks of treatment, mirtazapine induced downregulation of platelet alpha(2A)-adrenoceptors (up to 34%) and Galphai proteins (up to 28%), and the upregulation of GRK 2 (up to 30%). The results indicate that major depression is associated with reduced platelet GRK 2, suggesting that a defect of this kinase may contribute to the observed upregulation of alpha(2A)-adrenoceptors. Moreover, treatment with mirtazapine reversed this abnormality and induced downregulation of alpha(2A)-adrenoceptor/Galphai complex. The results support a role of supersensitive alpha(2A)-adrenoceptors in the pathogenesis and treatment of major depression.<p /><p>Language: en</p>",
language="en",
issn="0893-133X",
doi="10.1038/sj.npp.1300356",
url="http://dx.doi.org/10.1038/sj.npp.1300356"
}