Inositol phospholipid turnover in platelets of schizophrenic patients.
Abnormalities in blood cell membrane phospholipid composition and metabolism from schizophrenic patients have been reported by many groups of investigators. Among membrane phospholipids, inositol phospholipids are of special importance as they are involved in transduction system that generates second messengers such as inositol trisphosphate and diacylglycerol. Our studies on platelet inositol phospholipid turnover suggest a significant increase in platelet phosphatidylinositol 4,5-bisphosphate levels, an increased production of inositol trisphosphate in neuroleptic-treated and neuroleptic-free schizophrenic patients platelets and a reduced calcium release by thrombin in neuroleptic-treated schizophrenic patients platelets. The enhanced production of inositol trisphosphate may be due to an increase in its precursor phosphatidylinositol 4,5-bisphosphate with an associated desensitisation of the intracellular inositol trisphosphate receptor by neuroleptics, which may explain the diminished calcium response to thrombin in schizophrenic patients platelets.
Department of Psychiatry, Charing Cross and Westminster Medical School, London, UK.
I
I
Das
M A
MA
Essali
J
J
de Belleroche
S R
SR
Hirsch
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D015220:Calcium Channels; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008563:Membrane Lipids / Q000097:blood*; D008875:Middle Aged; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D015290:Second Messenger Systems; D013917:Thrombin / Q000494:pharmacology
D014150:Antipsychotic Agents; D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008563:Membrane Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D013917:Thrombin; D002118:Calcium