Density of guanine nucleotide-binding proteins in platelets of patients with major depression: Increased abundance of the G alpha(i2) subunit and down-regulation by antidepressant drug treatment

The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory G alpha(i), stimulatory G alpha(s), G alpha(q/11), and G beta) 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 G alpha(i2) was increased (41%) and that of G alpha(i3) decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (G alpha(s), G alpha(q/11), G beta) 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 G alpha(i2) protein (31%). Since platelet G alpha(i2) proteins mediated the signaling of alpha(2A)-adrenoceptors, the higher expression of G alpha(i2) is in line with the existence of supersensitivity of these receptors in major depression. (C) 1997 Society of Biological Psychiatry.