Adenosine A(2A) Receptor Modulates the Activity of Globus Pallidus Neurons in Rats.

Adenosine A(2A) Receptor Modulates the Activity of Globus Pallidus Neurons in Rats.
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DOI:
10.3389/fphys.2017.00897
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发表时间:
2017
影响因子:
4
通讯作者:
Chen L
Chen L
中科院分区:
医学2区
文献类型:
--
作者:
Diao HL;Xue Y;Han XH;Wang SY;Liu C;Chen WF;Chen L

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苍白球是基底神经节运动控制回路的中心核。形态学研究揭示了苍白球中腺苷A2A受体的表达。为了确定腺苷A2A受体对正常和帕金森大鼠苍白质神经元活性的调节作用,本研究进行了体内电生理和行为实验。胞外单单位记录显示,微压给药腺苷A2A受体激动剂CGS21680可调节苍白质放电活性。gaba能神经传递通过PKA通路参与cgs21680诱导的苍白质神经元的调节。此外,两种腺苷A2A受体拮抗剂KW6002或SCH442416的应用主要增加了苍白质神经元的自发放电,提示内源性腺苷系统通过腺苷A2A受体调节苍白质神经元的活性。最后,升高体摆动试验(EBST)显示,阴茎内微量注射腺苷A2A受体激动剂/拮抗剂分别诱导同侧/对侧偏置摆动。此外,电生理和行为学结果还显示,喹匹罗激活多巴胺D2受体可增强KW6002/ sch442416诱导的苍白质活动兴奋。喹匹罗与KW6002或SCH442416联合应用可减轻半帕金森大鼠的偏置摆动。基于目前的研究结果,我们得出结论,苍白叶腺苷A2A受体可能在帕金森病的治疗中有潜在的作用。
The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST) showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.
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