| Title | Phosphorylation of DARPP-32 (dopamine and cAMP regulated phosphoprotein of 32 KDa) induced by in vivo stimulation of adenosine A2A receptors in striatum of the dopamine-depleted weaver mouse | |
| Author | O. Pavlou¹, P. Poulou², A. Ekonomou²,³ and F. Angelatou²
1. Dept of Materials Science, School of Natural Sciences and 2. Dept. of Physiology, Medical School, University of Patras, Greece 3. Stem Cell Biology Lab., Wolfson Center, King’s College, London, UK |
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| Citation | Pavlou, O., Pavlou, P., Ekonomou, A., Angelatou, F.: Phosphorylation of DARPP-32 (dopamine and cAMP regulated phosphoprotein of 32 KDa) induced by in vivo stimulation of adenosine A2A receptors in striatum of the dopamine-depleted weaver mouse, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 298-300 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Weaver mutant, dopamine deficiency, A2A receptors, DARPP-32. | |
| Other Terms | review article | |
| Summary | Adenosine modulates neurotransmission in the basal ganglia acting via its A2A receptors. These are co-localized and interact functionally with D2 receptors, on the indirect pathway’s medium sized spiny neurons of the striatum, exerting opposing actions on neurotransmitter release, gene expression, and motor behavior. A recent study in our laboratory has shown that in vivo activation of adenosine A2A receptors elicits a strong expression of the immediate early gene (IEG) zif/268 in striatum and motor cortex of the weaver mouse, a genetic model of dopamine deficiency. In the present study, in order to clarify the signal transduction pathway mediating zif/268 induction via A2A adenosine receptors, we examined the phosphorylation state of DARPP-32 in striatal membranes of the weaver mouse after a single injection of CGS21680 (an A2A receptor agonist). DARPP-32 is a potent endogenous inhibitor of protein-phosphatase-1 (PP-1), which plays an obligatory role in dopaminergic transmission. Preliminary results demonstrated a significant upregulation of the phosphorylation levels of DARPP-32 in striatum of the weaver but not of the control mice. The phosphorylation levels of DARPP-32 were examined using Western blot analysis using a specific antibody directed against the phospho-Thr-34 moiety. These results indicate a super- sensitivity of A2A adenosine receptors, which under dopamine deficiency potentiate signaling, probably by activation of the A2A/cAMP/PKA/DARPP-32/PP-1 signal transduction pathway. We also investigate the pathways that lead to the IEG induction by examining the possible activation of other regulators, such as Mitogen Activated Protein Kinases. | |
| References | 1. Ekonomou et al.: Neuroscience 123: 1025 (2004)
2. Greengard et al.: Neuron 23: 435 (1999) 3. Svennigsson et al.: PNAS 97: 1856 (2000) |
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| Relative Papers |
Online ISSN 1011-6575
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