Elevated Platelet Calcium Mobilization and Nitric Oxide Synthase Activity May Reflect Abnormalities in Schizophrenic Brain

Schizophrenia has a diverse nature of clinical symptoms and a number of hypotheses have been suggested to explain its aetiological basis. In this study we have examined two aspects of membrane function, receptor-activated calcium mobilization and calcium activated nitric oxide synthase activity in s...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1995-07, Vol.212 (2), p.375-380
Main Authors: Das, I., Khan, N.S., Puri, B.K., Sooranna, S.R., Debelleroche, J., Hirsch, S.R.
Format: Article
Language:English
Subjects:
Adult
Amino Acid Oxidoreductases - antagonists & inhibitors
Amino Acid Oxidoreductases - blood
Arginine - analogs & derivatives
Arginine - pharmacology
Blood Platelets - drug effects
Blood Platelets - metabolism
Brain - metabolism
Calcium - blood
Female
Humans
Kinetics
Male
Middle Aged
Nitric Oxide - physiology
Nitric Oxide Synthase
omega-N-Methylarginine
Schizophrenia - blood
Schizophrenia - drug therapy
Schizophrenia - etiology
Thrombin - pharmacology
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Summary:Schizophrenia has a diverse nature of clinical symptoms and a number of hypotheses have been suggested to explain its aetiological basis. In this study we have examined two aspects of membrane function, receptor-activated calcium mobilization and calcium activated nitric oxide synthase activity in schizophrenic subjects. Thrombin induces mobilization of calcium ions from intracellular stores. The platelet response of drug naive schizophrenics was found to be significantly increased over a range of thrombin concentrations (0.01 to 0.60 U/ml) compared to control subjects. Possible involvement of nitric oxide (NO) in the aetiology of schizophrenia was investigated. NO has been functionally linked to both dopaminergic and glutamatergic systems both of which are strongly implicated in the biochemical pathology of schizophrenia. Nitric oxide synthase (NOS) activity was determined in platelets of controls, schizophrenic and panic disorder subjects. Enzyme activity was found to be significantly higher in platelets of drug naive schizophrenic subjects compared to controls, drug treated schizophrenics and panic disorder subjects. It is suggested that there is an imbalance of the calcium-induced L-arginine- nitric oxide pathway in platelets of schizophrenic subjects which may be modified by neuroleptic treatment. This imbalance may be mirrored in the central nervous system in particular at the NMDA receptor. It is possible that such a disturbance in the L-arginine-nitric oxide pathway may have pathological implications in the aetiology of schizophrenia.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1995.1980