کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4342247 | 1295861 | 2006 | 7 صفحه PDF | دانلود رایگان |
Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A2A receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa (DARPP-32) at Thr34 (the cAMP-dependent protein kinase [PKA] site) in striatopallidal neurons, and opposes dopamine D2 receptor signaling. In contrast, the role of adenosine A1 receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A1 receptors on D1, D2 and A2A receptor signaling using mouse neostriatal slices. An A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (100 nM), caused a transient increase, followed by a transient decrease, in DARPP-32 Thr34 phosphorylation. Our data support the following model for the actions of the A1 receptor agonist. The A1 receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D2 receptors of A2A receptor/Golf/cAMP/PKA signaling. The A1 receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic Gi mechanism, resulting in inhibition of D1 and A2A receptor-coupled Golf/cAMP/PKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A1 receptors play a major modulatory role in dopamine and adenosine receptor signaling.
Journal: Neuroscience - Volume 141, Issue 1, 2006, Pages 19–25