Activation of adenosine A2A and dopamine D1 receptors stimulates cyclic AMP dependent phosphorylation of DARPP-32 in distinct populations of striatal projection neurons

被引:101
作者
Svenningsson, P
Lindskog, M
Rognoni, F
Fredholm, BB
Greengard, P
Fisone, G [1 ]
机构
[1] Karolinska Inst, Dept Neurosci, Sect Neurophysiol, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Physiol & Pharmacol, Sect Mol Neuropharmacol, S-17177 Stockholm, Sweden
[3] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA
关键词
adenosine A(2A) receptors; dopamine D-1 receptors; DARPP-32; striatum; medium-sized spiny neurons; cyclic AMP-dependent protein kinase;
D O I
10.1016/S0306-4522(97)00510-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the striatum, adenosine A(2A) and dopamine D-1 receptors are segregated in striatopallidal and striatonigral projection neurons, respectively. In this study, we have examined the effects of activating adenosine A(2A) and dopamine D-1 receptors on the state of phosphorylation of DARPP-32 (dopamine-and cyclic AMP-regulated phosphoprotein of mel. wt 32,000), a potent endogenous regulator of protein phosphatase-1 that is highly expressed in striatal medium-sized spiny neurons. In rat striatal slices, the D-1 receptor agonist SKF 81297 and the A(2A) receptor agonist CGS 21680 transiently increased the levels of phosphorylated DARPP-32 in a concentration-dependent manner. In the same preparation, the two agonists were also able to induce a significant increase in cyclic AMP formation. When striatal slices were incubated with a combination of CGS 21680 and SKF 81297, the effects of the two agonists on both DARPP-32 phosphorylation and cyclic AMP formation were additive. The maximal effects of SKF 81297 and CGS 21680 on DARPP-32 phosphorylation were of similar magnitude, and were completely abolished by the cyclic AMP-dependent protein kinase inhibitor, Rp-cAMPS. The present results show that DARPP-32 phosphorylation in the striatum is stimulated by adenosine, acting on A(2A) receptors, and dopamine, acting on D-1 receptors, and that cyclic AMP is the mediator in both cases. Our data also suggest that dopamine and adenosine regulate the state of phosphorylation of DARPP-32 in distinct sub-populations of medium-sized spiny neurons expressing dopamine D-1 and adenosine A(2A) receptors, respectively. (C) 1998 IBRO. Published by Elsevier Science Ltd.
引用
收藏
页码:223 / 228
页数:6
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