Phosphoinositide signalling system in platelets of schizophrenic patients and the effect of neuroleptic therapy.
Alterations in the phosphoinositide signalling system have been proposed as a possible biological marker of schizophrenia. We studied the levels of inositol 1,4,5-trisphosphate (IP3), cytosolic Ca2+ concentrations ([Ca2+]i), and the incorporation of [32P]-orthophosphate into inositol phospholipids and phosphatidic acid (PA) in blood platelets of neuroleptic-treated schizophrenics in comparison with controls. The [Ca2+]i was significantly higher in platelets of one month neuroleptic-treated patients (155+/-5.8 nM) in comparison with controls (95+/-5.4 nM). Neuroleptic therapy decreased the [Ca2+]i, but even after long-term therapy it remained significantly higher (114+/-5.7 nM) than in controls. Differences were also found in the level of IP3 between controls (30+/-4.0 pmol/10(9) platelets), drug-free schizophrenics (52+/-9.0 pmol/10(9) platelets) and treated patients (50+/-6.0 pmol/10(9) platelets). The increased turnover of PA was observed in platelets of neuroleptic-treated schizophrenic patients. The study suggests that the regulation of calcium homeostasis and pathways involved in the phosphoinositide signalling system are altered in the platelets of schizophrenics. Neuroleptic therapy did not remove the observed changes in [Ca2+]i and IP3 levels.
Rípová
D
D
Laboratory of Biochemistry, Prague Psychiatric Center, Czech Republic. ripova@pcp.lf3.cuni.cz
Strunecká
A
A
Platilová
V
V
Höschl
C
C
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010712:Phosphatidic Acids / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000097:blood* / Q000378:metabolism / Q000502:physiology*; D010761:Phosphorus Radioisotopes; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D015398:Signal Transduction; D013997:Time Factors
D014150:Antipsychotic Agents; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; C037178:phosphatidylinositol 4-phosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium