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Up‐Regulation of Immunolabeled α 2A ‐Adrenoceptors,G i Coupling Proteins, and Regulatory Receptor Kinases in the Prefrontal Cortex of Depressed Suicides
Author(s) -
GarcíaSevilla Jesús A.,
Escribá Pablo V.,
Ozaita Andrés,
La Harpe Romano,
Walzer Claude,
Eytan Ariel,
Guimón José
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720282.x
Subject(s) - prefrontal cortex , g protein coupled receptor kinase , receptor , medicine , endocrinology , adrenergic receptor , cortex (anatomy) , neuroscience , biology , psychology , g protein , cognition
: Suicide and depression are associated with an increaseddensity of α 2 ‐adrenoceptors (radioligand receptor binding) inspecific regions of the human brain. The function of these inhibitoryreceptors involves various regulatory proteins (G i couplingproteins and G protein‐coupled receptor kinases, GRKs), which work in concertwith the receptors. In this study we quantitated in parallel the levels ofimmunolabeled α 2A ‐adrenoceptors and associated regulatoryproteins in brains of suicide and depressed suicide victims. Specimens of theprefrontal cortex (Brodmann area 9) were collected from 51 suicide victims and31 control subjects. Levels of α 2A ‐adrenoceptors,Gα 1/2 proteins, and GRK 2/3 were assessed by immunoblottingtechniques by using specific polyclonal antisera and the immunoreactiveproteins were quantitated by densitometry. Increased levels ofα 2A ‐adrenoceptors (31‐40%), Gα 1/2 proteins(42‐63%), and membrane‐associated GRK 2/3 (24‐32%) were found in theprefrontal cortex of suicide victims and antidepressantfree depressed suicidevictims. There were significant correlations between the levels of GRK 2/3(dependent variable) and those of α 2A ‐adrenoceptors andGα 1/2 proteins (independent variables) in the same brainsamples of suicide victims ( r = 0.56, p = 0.008) anddepressed suicide victims ( r = 0.54, p = 0.041). Antemortemantidepressant treatment was associated with a significant reduction in thelevels of Gα 1/2 proteins (32%), but with modest decreases inthe levels of α 2A ‐adrenoceptors (6%) and GRK 2/3 (18%) inbrains of depressed suicide victims. The increased levels in concert ofα 2A ‐adrenoceptors, Gα 1/2 proteins, and GRK2/3 in brains of depressed suicide victims support the existence ofsupersensitive α 2A ‐adrenoceptors in subjects with major depression.