Abstract
Changes in the phosphoinositide (PPI) signal transduction system induced by E-5842, a new sigma(1) (sigma(1)) receptor ligand and potential atypical antipsychotic, were studied in the rat frontal cortex, hippocampus and striatum. Acute treatment with E-5842 increased phospholipase C (PLC) activity in the striatum and the hippocampus. Chronic treatment with E-5842 induced an increase in the activity of PLC in the frontal cortex and the striatum. Similar up-regulation of the activity of the enzyme was also observed in rat frontal cortex membranes in presence of GTPgammaS. After chronic treatment with E-5842, it was also observed a significant increase of the immunoreactivity levels of G(q/11)alpha in the frontal cortex. Our results suggest that part of the antipsychotic effects of E-5842 could be related to the regulation of the PPI signal transduction pathway, especially after a prolonged treatment.
MeSH terms
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Animals
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Antipsychotic Agents / pharmacology*
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Brain / cytology
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Brain / drug effects*
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Brain / enzymology
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Frontal Lobe / cytology
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Frontal Lobe / drug effects
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Frontal Lobe / metabolism
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GTP-Binding Protein alpha Subunits, Gq-G11
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GTP-Binding Proteins / drug effects*
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GTP-Binding Proteins / metabolism
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Male
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Neostriatum / cytology
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Neostriatum / drug effects
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Neostriatum / metabolism
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Phosphatidylinositols / metabolism*
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Pyridines / pharmacology*
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Rats
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Rats, Wistar
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Receptors, sigma / drug effects*
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Receptors, sigma / metabolism
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Sigma-1 Receptor
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Signal Transduction / drug effects*
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Signal Transduction / physiology
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Triazoles / pharmacology*
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Type C Phospholipases / drug effects*
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Type C Phospholipases / metabolism
Substances
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Antipsychotic Agents
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E 5842
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Phosphatidylinositols
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Pyridines
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Receptors, sigma
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Triazoles
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Type C Phospholipases
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GTP-Binding Proteins
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GTP-Binding Protein alpha Subunits, Gq-G11