Platelet phosphoinositide signaling system. An overstimulated pathway in depression

In order to test a possible depression-associated defect in signal transduction, platelet alpha2-adrenergic-mediated phosphoinositide (PI) hydrolysis is was measured, both in drug-free major depressed patients and in control healthy subjects. Results that express phospholipase C activity have shown significant increase in the metabolites of epinephrine-stimulated tritiated phosphatidyl-4,5-biphosphate (3H-PIP2) with respect to basal activity (saline-stimulated), Thrombin (2 units) and 10 mM sodium fluoride (NaF) also induced an increase in 3H-PIP2 metabolites, These increases were potentiated in drug-free depressed patients both in epinephrine-and thrombin-stimulated platelets. In contrast, sodium fluoride, which directly stimulates G protein without receptor interaction, did not differentiate between patients and controls with respect to PI hydrolysis, This result suggests a possible depression-associated defect in heterologous receptor-G protein interaction.