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

被引:26
作者
Kim, Se Hyun [1 ]
Seo, Myoung Suk [2 ]
Jeon, Won Je [2 ]
Yu, Hyun-Sook [2 ]
Park, Hong Geun [2 ]
Jung, Gyung-Ah [2 ]
Lee, Hee Young [2 ]
Kang, Ung Gu [1 ,3 ]
Kim, Yong Sik [1 ,3 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, Seoul 110744, South Korea
[2] Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea
[3] Seoul Natl Univ, Coll Med, Inst Human Behav Med, Seoul 110744, South Korea
关键词
Antipsychotics; mitogen-activated protein kinase; protein serine/threonine phosphatase 2A;
D O I
10.1017/S1461145707008292
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:509 / 517
页数:9
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