Increased arachidonic acid induced platelet chemiluminescence indicates cyclooxygenase overactivity in schizophrenic subjects.
Platelets were found to emit a burst of chemiluminescence during incubation with arachidonic or linoleic acid. This chemiluminescence response may indicate activation of the enzyme prostaglandin synthase in the arachidonate-induced platelet chemiluminescence as it is inhibited by aspirin. Stimulation of platelets with arachidonic acid and linoleic acid induced a concentration dependent chemiluminescence response. Platelets from drug naive schizophrenic subjects showed significantly increased arachidonic acid metabolism compared to control subjects. No significant difference was observed between schizophrenic and control subjects in the chemiluminescence response to linoleic acid. In schizophrenic subjects treated with neuroleptic drugs the overactive arachidonic acid response was normalized. Linoleic acid chemiluminescence response was unaffected by neuroleptic treatment. Hyperactive cyclooxygenase activity may reflect a similar condition in the brain and implicates prostaglandin pathway abnormalities in the pathogenesis of schizophrenia.
Das
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I
Department of Psychiatry, Imperial College School of Medicine, London, UK.
Khan
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NS
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood* / Q000201:enzymology; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D013469:Sulpiride; D019787:Linoleic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin