Modification of adenosine extracellular levels and adenosine A2A receptor mRNA by dopamine denervation
Modification of adenosine extracellular levels and adenosine A2A receptor mRNA by dopamine denervation
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DOI：
10.1016/s0014-2999(02)01818-6
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发表时间：
2002-06-20
影响因子：
5
通讯作者：
Morelli, M
中科院分区：
文献类型：
--
作者：
Pinna, A;Corsi, C;Morelli, M
腺苷A(2A)受体拮抗剂已被提议作为治疗帕金森病的有效疗法。为了探讨多巴胺去神经可能对腺苷 A(2A) 传递产生改变的可能性，我们测量了内侧前脑束单侧输注 6-羟基多巴胺的大鼠纹状体中腺苷和腺苷 A(2A) 受体 mRNA 的细胞外浓度。输注 6-羟基多巴胺 15 天后，通过体内微透析测量，多巴胺去神经纹状体中的细胞外腺苷水平显着降低（-35%）。在腺苷水平降低时，通过原位杂交测量，观察到纹状体腺苷 A(2A) 受体 mRNA 水平增加 (+20%)。黑质纹状体多巴胺神经元变性后腺苷 A(2A) 传递的改变为腺苷 A(2A) 受体拮抗剂治疗帕金森病的有效性奠定了潜在的神经基础。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Adenosine A(2A) receptor antagonists have been proposed as an effective therapy in the treatment of Parkinson's disease. To explore the possibility that dopamine denervation may produce modifications in adenosine A(2A) transmission, we measured the extracellular concentration of adenosine and adenosine A(2A) receptor mRNA in the striatum of rats infused unilaterally with 6-hydroxydopamine in the medial forebrain bundle. Fifteen days after 6-hydroxydopamine infusion, extracellular adenosine levels, measured by in vivo microdialysis, were significantly lower (-35%) in the dopamine-denervated striatum. At the time of the decrease in adenosine levels, an increase in striatal adenosine A(2A) receptor mRNA levels (+20%), measured by in situ hybridization, was observed. Modifications in adenosine A(2A) transmission, following nigrostriatal dopamine neuron degeneration, establish a potential neural basis for the effectiveness of adenosine A(2A) receptor antagonists in the treatment of Parkinson's disease. (C) 2002 Elsevier Science B.V. All rights reserved.