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Haloperidol regulates the phosphorylation level of the MEK-ERK-p90RSK signal pathway via protein phosphatase 2A in the rat frontal cortex

Cited 23 time in Web of Science Cited 23 time in Scopus
Authors
Kim, Se Hyun; Seo, Myoung Suk; Jeon, Won Je; Yu, Hyun-Sook; Park, Hong Geun; Jung, Gyung-Ah; Lee, Hee Young; Kang, Ung Gu; Kim, Yong Sik
Issue Date
2008-02-15
Publisher
Cambridge University Press
Citation
International Journal of Neuropsychopharmacology 11, 509-517
Keywords
AnimalsAntipsychotic Agents/*pharmacologyBlotting, WesternDose-Response Relationship, DrugExtracellular Signal-Regulated MAP Kinases/genetics/*physiologyHaloperidol/*pharmacologyImmunoprecipitationMaleMitogen-Activated Protein Kinases/genetics/*physiologyPhosphoprotein Phosphatases/metabolismPhosphorylation/drug effectsPrefrontal Cortex/drug effects/enzymology/*physiologyProtein Phosphatase 2/*physiologyProto-Oncogene Proteins c-raf/genetics/physiologyRatsRats, Sprague-DawleyRibosomal Protein S6 Kinases, 90-kDa/genetics/*physiologySignal Transduction/*drug effectsraf Kinases/physiology
Abstract
Haloperidol, a classical antipsychotic drug, affects the extracellular signal-regulated kinase (ERK) pathway in the brain. However, findings are inconsistent and the mechanism by which haloperidol regulates ERK is poorly understood. Therefore, we examined the ERK pathway and the related protein phosphatase 2A (PP2A) in detail after haloperidol administration. Haloperidol (0.5 and 1 mg/kg) induced biphasic changes in the phosphorylation level of mitogen-activated protein kinase kinase (MEK), ERK, and p90 ribosomal S6 kinase (p90RSK) without changing Raf-1 phosphorylation. Fifteen minutes after haloperidol administration, MEK-ERK-p90RSK phosphorylation increased, whilst PP2A activity decreased. At 60 min, the reverse was observed and the binding of PP2A to MEK and ERK increased. Higher dosages of haloperidol (2 and 4 mg/kg), affected neither MEK-ERK-p90RSK phosphorylation nor PP2A activity. Accordingly, PP2A regulates acute dose- and time-dependent changes in MEK-ERK-p90RSK phosphorylation after haloperidol treatment. These findings suggest the involvement of a dephosphorylating mechanism in the acute action of haloperidol.
ISSN
1461-1457 (Print)
Language
English
URI
https://hdl.handle.net/10371/62001
DOI
https://doi.org/10.1017/S1461145707008292
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College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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