Role of adenosine A1, receptors in the modulation of dopamine D1, and adenosine A2a receptor signaling in the neostriatum

被引:45
作者
Yabuuchi, K.
Kuroiwa, M.
Shuto, T.
Sotogaku, N.
Snyder, G. L.
Higashi, H.
Tanaka, M.
Greengard, P.
Nishi, A.
机构
[1] Kurume Univ, Sch Med, Dept Pharmacol, Kurume, Fukuoka 8300011, Japan
[2] Oita Univ, Fac Med, Yufu, Oita 8795593, Japan
[3] Intracellular Therapies Inc, New York, NY 10032 USA
[4] Kurume Univ, Sch Med, Dept Physiol, Kurume, Fukuoka 8300011, Japan
[5] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA
关键词
DARPP-32; dopamine D2 receptors; G(olf); G(i); PKA;
D O I
10.1016/j.neuroscience.2006.04.047
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A(2A) receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein Of M-r 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 A(1) receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A, receptors on D-1, D-2 and A(2A) receptor signaling using mouse neostriatal slices. An A, receptor agonist, 2-chloro-N-6-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 A, receptor agonist. The A, receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D-2 receptors of A(2A) receptor/G(olf)/cAMP/PKA signaling. The A(1) receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic G, mechanism, resulting in inhibition of D-1 and A(2A) receptor-coupled G(olf)/cAMPIPKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A(1) receptors play a major modulatory role in dopamine and adenosine receptor signaling. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:19 / 25
页数:7
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