Epinephrine- and thrombin-stimulated high-affinity GTPase activity in platelet membranes from patients with psychiatric disorders

Abstract 

Although heterotrimeric guanine nucleotide-binding regulatory (G) proteins have been implicated in the pathophysiology of mental illnesses (especially mood disorders), direct evidence has been scarce. This study was designed to reveal possible abnormalities of receptor-coupled G protein function in platelets in patients with psychiatric disorders such as depression and schizophrenia. The functional status of α_2A-adrenergic receptor-coupled G_i2 and thrombin receptor-coupled G proteins (G_i2+G_q) was determined by the increase in high-affinity GTPase activity in response to epinephrine and thrombin, respectively, in platelet membranes from 18 patients with mood disorders (15 unipolar and three bipolar subtype), 13 schizophrenic patients, four neurotic patients and 29 healthy control subjects. Neither α_2A-adrenergic receptor-coupled G_i2 nor thrombin receptor-coupled G_q was functionally altered in platelets from psychiatric patients compared with control subjects. No significant correlation was observed between these biochemical measures in platelets and severity of psychopathological symptoms. The functional coupling efficiency of G proteins with receptors appears intact, at least between α_2A-adrenergic receptors and G_i2, and between thrombin receptors and G_q, in platelets from patients with psychiatric disorders.

Keywords:  G protein, Blood platelets, α_2A-Adrenergic receptor, Thrombin receptor, Mood disorder, Schizophrenia