Long-term exposure to the atypical antipsychotic olanzapine differently up-regulates extracellular signal-regulated kinases 1 and 2 phosphorylation in subcellular compartments of rat prefrontal cortex
Articolo
Data di Pubblicazione:
2006
Citazione:
Long-term exposure to the atypical antipsychotic olanzapine differently up-regulates extracellular signal-regulated kinases 1 and 2 phosphorylation in subcellular compartments of rat prefrontal cortex / F. Fumagalli, A. Frasca, M. Sparta, F. Drago, G. Racagni, MA. Riva. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 69:4(2006), pp. 1366-1372.
Abstract:
Antipsychotics are the drugs of choice for the treatment of schizophrenia. Besides blocking monoamine receptors, these mols. affect intracellular signaling mechanisms, resulting in long-term synaptic alterations. Western blot anal. was used to investigate the effect of long-term administration (14 days) with the typical antipsychotic haloperidol and the atypical olanzapine on the expression and phosphorylation state of extracellular signal-related kinases (ERKs) 1 and 2 (ERK1/2), proteins involved in the regulation of multiple intracellular signaling cascades. A single injection of both drugs produced an overall decrease in ERK1/2 phosphorylation in different subcellular compartments. Conversely, long-term treatment with olanzapine, but not haloperidol, increased ERK1/2 phosphorylation in the prefrontal cortex in a compartment-specific and time-dependent fashion. In fact, ERK1/2 phosphorylation was elevated in the nuclear and cytosolic fractions 2 h after the last drug administration, whereas it was enhanced only in the membrane fraction when the animals were killed 24 h after the last injection. This effect might be the result of an activation of the mitogen-activated protein kinase pathway, because the phosphorylation of extracellular signal-regulated kinase kinase 1/2 was also increased by long-term olanzapine administration. Our data demonstrate that long-term exposure to olanzapine dynamically regulates ERK1/2 phosphorylation in different subcellular compartments, revealing a novel mechanism of action for this atypical agent and pointing to temporally sepd. locations of signaling events mediated by these kinases after long-term olanzapine administration
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Antipsychotics; Schizophrenia; Signal transduction (long-term exposure to the atypical antipsychotic olanzapine differently up-regulates extracellular signal-regulated kinases 1 and 2 phosphorylation in subcellular compartments of rat prefrontal cortex); Brain (prefrontal cortex; long-term exposure to the atypical antipsychotic olanzapine differently up-regulates extracellular signal-regulated kinases 1 and 2 phosphorylation in subcellular compartments of rat prefrontal cortex); Phosphorylation (protein; long-term exposure to the atypical antipsychotic olanzapine differently up-regulates extracellular signal-regulated kinases 1 and 2 phosphorylation in subcellular compartments of rat prefrontal cortex); Neurotransmission (synaptic; long-term exposure to the atypical antipsychotic olanzapine differently up-regulates extracellular signal-regulated kinases 1 and 2 phosphorylation in subcellular compartments of rat prefrontal cortex)
Elenco autori:
F. Fumagalli, A. Frasca, M. Sparta, F. Drago, G. Racagni, MA. Riva
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