Second messenger imbalance hypothesis of schizophrenia.
Based on the results of studies on intracellular signaling in platelets of schizophrenics, an imbalance of the second messenger system is proposed: Diacylglycerol (DG), which activates protein kinase C (PKC), was increased, while adenylate cyclase (AC)-cAMP function was decreased. It is proposed that the increased DG/PKC function may entail a decrease in inositol 1,4,5-trisphosphate (IP3)/Ca2+ function and lowering of phosphoinositide turnover. If such a pathological intracellular signaling takes place in the brain, it may cause a distorted balance of protein activation via phosphorylation in neurons, resulting in some of the deficits of schizophrenia. Neuroleptics have been reported to antagonize the above-mentioned pathological processes of intracellular signaling. The imbalance hypothesis of the DG/PKC pathway and AC-cAMP pathway is not inconsistent with the dopamine hypothesis of schizophrenia, because dopamine receptor stimulation is indirectly related to reduction in IP3/Ca2+ function and lowering of phosphoinositide metabolism.
Psychiatry Service, Self-Defence Forces Central Hospital, Tokyo, Japan.
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Kaiya
D014150:Antipsychotic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011954:Receptors, Dopamine / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D009435:Synaptic Transmission
C011439:1,2-diacylglycerol; D014150:Antipsychotic Agents; D004075:Diglycerides; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D011954:Receptors, Dopamine; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium