Density of Guanine Nucleotide-Binding Proteins in Platelets of Patients with Major Depression: Increased Abundance of the Gα i2 Subunit and Down-Regulation by Antidepressant Drug Treatment

Abstract

The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory Gα i, stimulatory Gα s, Gα q/11, and Gβ) in platelets of unipolar depressed patients to assess the status of these signal transduction proteins in depression and the effects of antidepressant drug treatment. Blood platelets were collected from 22 drug-free depressed patients and 22 age- and sex-matched healthy controls. The levels of the various G protein subunits were assessed by immunoblotting techniques. The immunoreactivity of Gα i2 was increased (41%) and that of Gα i3 decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (Gα s, Gα q/11, Gβ) did not change significantly with respect to those of control subjects. Chronic administration of cyclic antidepressant drugs (citalopram, clomipramine, imipramine) decreased the immunoreactivity of the up-regulated Gα i2 protein (31%). Since platelet Gα i2 proteins mediate the signaling of α 2A-adrenoceptors, the higher expression of Gα i2 is in line with the existence of supersensitivity of these receptors in major depression.