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.

[1]  D. V. van Kammen,et al.  Incorporation of 3H-arachidonic acid into platelet phospholipids of patients with schizophrenia. , 1996, Prostaglandins, leukotrienes, and essential fatty acids.

[2]  Jeffrey K. Yao,et al.  Abnormal incorporation of arachidonic acid into platelets of drug-free patients with schizophrenia , 1996, Psychiatry Research.

[3]  M. Berridge.  Inositol trisphosphate and calcium signalling , 1993, Nature.

[4]  H. Kaiya.  Second messenger imbalance hypothesis of schizophrenia. , 1992 .

[5]  S. Hirsch,et al.  Inositol phospholipid turnover in platelets of schizophrenic patients. , 1992, Prostaglandins, Leukotrienes and Essential Fatty Acids.

[6]  D. V. van Kammen,et al.  Increased turnover of platelet phosphatidylinositol in schizophrenia. , 1992, Prostaglandins, leukotrienes, and essential fatty acids.

[7]  R. Tandon,et al.  Abnormal phosphoinositide turnover in schizophrenia , 1991, Biological Psychiatry.

[8]  S. Hirsch,et al.  The platelet polyphosphoinositide system in Schizophrenia: The effects of neuroleptic treatment , 1990, Biological Psychiatry.

[9]  S. Hirsch,et al.  Regulation of the platelet polyphosphoinositide system by antipsychotic drugs: A specific neuroleptic action , 1990, Schizophrenia Research.

[10]  S. Nakashima,et al.  Accumulation of diacylgylcerol in platelet phosphoinositide turnover in Schizophrenia: A biological marker of good prognosis? , 1989, Biological Psychiatry.

[11]  Michael J. Berridge,et al.  Inositol trisphosphate, a novel second messenger in cellular signal transduction , 1984, Nature.

[12]  T. Rink,et al.  What turns platelets on , 1984 .

[13]  B. Agranoff,et al.  Renewed interest in the polyphosphoinositides , 1984 .

[14]  J. Hawthorne.  Polyphosphoinositide metabolism in excitable membranes , 1983, Bioscience reports.

[15]  E. Lapetina.  Metabolism of inositides and the activation of platelets. , 1983, Life sciences.

[16]  M. Berridge,et al.  Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. , 1982, The Biochemical journal.

[17]  K. Wirtz,et al.  Pituitary hormones influence polyphosphoinositide metabolism in rat brain , 1979, FEBS letters.

[18]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[19]  V. Němcová,et al.  Phospholipids and calcium alterations in platelets of schizophrenic patients. , 1997, Physiological research.

[20]  J. Luzio,et al.  Cell signalling : Experimental strategies , 1991 .

[21]  S. Snyder,et al.  Second messenger systems and psychoactive drug action: focus on the phosphoinositide system and lithium. , 1989, The American journal of psychiatry.

[22]  P. Folk,et al.  Effect of chlorpromazine on inositol-lipid signalling system in human thrombocytes. , 1987, Physiologia Bohemoslovaca.

[23]  L. Haškovec,et al.  Incorporation of [–3–2P]-orthophosphate into phosphoinositides in platelets of depressive patients before and after 10-day lithium administration. , 1987 .