Abnormal incorporation of arachidonic acid into platelets of drug-free patients with schizophrenia.
Incorporation of [3H]arachidonic acid (AA) into resting platelets was studied in samples from schizophrenic patients before and after haloperidol withdrawal, and from normal subjects. Eicosanoid biosynthesis was subsequently evaluated in prelabeled platelets by sequential events of thrombin activation. The total incorporation of [3H]AA in drug-free patients was significantly lower than in the same individuals during haloperidol treatment as well as in normal volunteers. No significant difference of [3H]AA incorporation was demonstrated between relapsed and nonrelapsed drug-free patients. The majority of 3H-labeled lipids were found in platelet phospholipids, and < 10% of incorporated lipids were found in free AA, diacylglycerol (DAG), triacylglycerol, and hydroxyeicosatetraenoic acid (HETE) of normal resting platelets. After thrombin activation, however, there was an increased 3H-labeling in 12-HETE, 12-hydroxyheptadecatrienoic acid, and thromboxane B2. The thrombin-induced formation of eicosanoids was found to be significantly higher in haloperidol-treated patients than in normal volunteers. This increased formation of eicosanoids appeared to be normalized after haloperidol withdrawal. In addition, both haloperidol-treated and drug-free patients showed increased 3H-labeling in thrombin-induced DAG compared with normal volunteers. Such an increase in the second messenger formation may be due, at least in part, to an increased turnover of membrane phosphoinositides via phospholipase C reaction. The present data support our previous findings demonstrating altered membrane dynamics in schizophrenia.
Yao
J K
JK
Department of Psychiatry, University of Pittsburgh Medical Center, PA 15206, USA.
van Kammen
D P
DP
Gurklis
J A
JA
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000097:blood* / Q000378:metabolism; D001792:Blood Platelets; D002851:Chromatography, High Pressure Liquid; D004075:Diglycerides / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood; D015539:Platelet Activation; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D015290:Second Messenger Systems / Q000187:drug effects; D013917:Thrombin / Q000187:drug effects
D014150:Antipsychotic Agents; D004075:Diglycerides; D015777:Eicosanoids; D008563:Membrane Lipids; D010743:Phospholipids; D016718:Arachidonic Acid; D013917:Thrombin; D006220:Haloperidol