DARPP-32 anal modulation of cAMP signaling:: involvement in motor control and levodopa-induced dyskinesia

被引：42

作者：

Håkansson, K ^{[1
]}

Lindskog, M ^{[1
]}

Pozzi, L ^{[1
]}

Usiello, A ^{[1
]}

Fisone, G ^{[1
]}

机构：

[1] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden

来源：

PARKINSONISM & RELATED DISORDERS | 2004年 / 10卷 / 05期

关键词：

basal ganglia; striatum; dopamine D-1; receptors; adenosine A(2A) receptors; caffeine; phosphorylation;

D O I：

10.1016/j.parkreldis.2004.02.010

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is abundantly expressed in the medium spiny neurons of the striatum. Phosphorylation catalysed by cAMP-dependent protein kinase (PKA) converts DARPP-32 into an inhibitor of protein phosphatase-1. In contrast, phosphorylation catalysed by cyclin dependent kinase-5 on Thr75 converts DARPP-32 into an inhibitor of PKA. Changes in the state of phosphorylation of DARPP-32 reinforce the behavioral effects produced by stimulation or inhibition of the cAMP pathway. Dopamine, via D-1 receptors, and adenosine, via A(2A) receptors, affect motor behavior by acting on medium spiny neurons, via G(olf) mediated stimulation of the cAMP signaling cascade. The involvement of DARPP-32 in dopamine and adenosine transmission and the possible role played by abnormal regulation of DARPP-32 phosphorylation in levodopa-induced dyskinesia are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：281 / 286

页数：6

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