Increased turnover of platelet phosphatidylinositol in schizophrenia.
The potential role of receptor-stimulated phosphatidylinositol (PI) hydrolysis in a signal transduction mechanism has been increasingly recognized. Earlier studies have suggested a defect in alpha-adrenergic receptor function in the platelets of schizophrenic patients. Little is known, however, about the mechanisms for PI synthesis, breakdown, and regulation in schizophrenia. The present study was undertaken to investigate the metabolic turnover of inositol phospholipids and inositol phosphates by incorporation of [3H]myoinositol or [32P]orthophosphate into resting and activated platelets of normal controls and schizophrenic patients with and without neuroleptic treatment. After 5 h incubation at 37 degrees C, the majority of [3H]myoinositol was incorporated into platelet PI. Following thrombin-induced platelet activation, there was rapid formation of 3H-labeled inositol phosphates (IPs) with inositol monophosphate (IP1) being the most abundant product. The thrombin-induced formation of platelet IPs was found significantly higher in both haloperidol-stabilized and drug-free schizophrenics than in normal control subjects. When platelets were prelabeled with [32P]orthophosphates, thrombin-induced formation of phosphatidic acid (PA) was also significantly higher in haloperidol-stabilized schizophrenics than in normal controls. It is thought that thrombin-induced platelet activation is mediated through hydrolysis of polyphosphoinositides (poly-PI). The present data thus may reflect an increased signal transduction in schizophrenia, which is mediated through neuroleptic-regulated inositol phospholipid hydrolysis.
Department of Veterans Affairs Medical Center, University of Pittsburgh, PA 15206.
J K
JK
Yao
P
P
Yasaei
D P
DP
van Kammen
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007294:Inositol / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000493:pharmacokinetics; D010716:Phosphatidylinositols / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D015290:Second Messenger Systems / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
D014150:Antipsychotic Agents; D010710:Phosphates; D010716:Phosphatidylinositols; D007294:Inositol; D013917:Thrombin; D006220:Haloperidol