Incorporation of 3H-arachidonic acid into platelet phospholipids of patients with schizophrenia.
Incorporation of 3H-arachidonic acid (AA) into resting platelets was carried out in normal control subjects as well as in schizophrenic patients before and after haloperidol (HD) withdrawal. Metabolic turnover of membrane phospholipids was subsequently evaluated in prelabelled platelets at various time intervals after thrombin activation. 3H-AA was mainly incorporated into phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylserine (PS) of resting platelets. Very minute amounts of 3H-labelling were found in phosphatidic acid (PA). Following thrombin activation, however, substantial amounts of 3H-labelling were found in PA. Such an increase in thrombin-induced PA formation was not reduced in schizophrenic patients both receiving and not receiving HD treatment. Increased labelling has been found in platelet diacylglycerol (DAG) after thrombin activation. It is therefore not likely that a decreased DAG kinase activity contributes to the accumulation of DAG. However, the thrombin-induced PA production was temporally associated with a decreased 3H-labelling in PI, but not in PC, PS and PE. The present data taken together with our previous findings suggest that the increased production of second messengers (DAG, PA and inositol phosphates) in schizophrenia may result from an increased phospholipase C (PLC) activity in schizophrenia, because thrombin-induced platelet activation is mediated by polyphosphoinositide hydrolysis through the G-protein activation.
Department of Veterans Affairs Medical Center, Pittsburgh, PA, USA.
J K
JK
Yao
D P
DP
van Kammen
D001095:Arachidonic Acids / Q000032:analysis / Q000096:biosynthesis*; D001792:Blood Platelets / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008563:Membrane Lipids / Q000096:biosynthesis* / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis* / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D001095:Arachidonic Acids; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D018129:Phosphatidylinositol Phosphates; D010718:Phosphatidylserines; D010743:Phospholipids; D014316:Tritium; D013917:Thrombin