Platelet phosphoinositide signaling system: an overstimulated pathway in depression.
In order to test a possible depression-associated defect in signal transduction, platelet alpha 2-adrenergic-mediated phosphoinositide (PI) hydrolysis 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.
Karege
F
F
University of Geneva Institutes of Psychiatry, Division of Neuropsychiatry, Chêne-Bourg (Geneva), Switzerland.
Bovier
P
P
Rudolph
W
W
Gaillard
J M
JM
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D003863:Depression / Q000097:blood*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010716:Phosphatidylinositols; D015016:Yohimbine; D013917:Thrombin; D004837:Epinephrine