Differential Effects of the Antipsychotics Haloperidol and Clozapine on G Protein Measures in Mononuclear Leukocytes of Patients with Schizophrenia
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Aims: Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins were previously implicated in the pathophysiology and treatment of mood and other neuropsychiatric disorders. Recently we showed that untreated patients with schizophrenia have a significantly elevated dopamine-induced Gs protein function which is correlated with the severity of the psychotic symptoms. In contrast, an inverse picture with reduction in the function and the immunoreacitivity of Gs protein was detected in patients with Parkinson's disease. The present study aims at investigating the effect of antipsychotic medications on dopamine-induced Gs protein hyperfunction in schizophrenia comparing the classical antipsychotic haloperidol and the newer antipsychotic clozapine, which is devoid of extrapyramidal side effects, on G protein measures.Methods: G protein functional measurements coupled to -adrenergic, muscarinic, and dopamine receptors were undertaken through bacterial toxin sensitive, agonistenhanced [3H]-Gpp(NH)p binding capacity, substantiated by quantitative measures of Gs, Gi, and G subunit proteins through immunoblot analysis in mononuclear leukocytes obtained from patients with schizophrenia under haloperidol, or clozapine treatments in comparison with untreated patients with schizophrenia and healthy volunteers.
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