Adenosine A2A receptor antagonism increases striatal glutamate outflow in dopamine-denervated rats
Adenosine A2A receptor antagonism increases striatal glutamate outflow in dopamine-denervated rats
复制标题
DOI：
10.1016/s0014-2999(03)01352-9
复制
发表时间：
2003-03-07
影响因子：
5
通讯作者：
Pedata, F
中科院分区：
文献类型：
--
作者：
Corsi, C;Pinna, A;Pedata, F
本研究旨在通过体内微透析研究腺苷A（2A）受体拮抗剂7-（2-苯乙基）-5-氨基-2-（2-呋喃基）-吡唑并[4，3-e]-1，2，4-三唑并[1，5-c]嘧啶（SCH 58261）对单侧6-羟基多巴胺输注大鼠纹状体谷氨酸流出的影响。两个垂直的微透析探针植入双侧在失神经支配的纹状体和完整的纹状体。通过高效液相色谱法（HPLC）测定透析液中的谷氨酸浓度。通过微透析纤维输注腺苷A（2A）受体拮抗剂SCH 58261（50 nM）显著增加了去神经纹状体的谷氨酸流出，同时减少了完整纹状体的谷氨酸流出。SCH 58261对完整和6-羟基多巴胺损伤纹状体中谷氨酸流出的相反作用可能归因于阻断位于纹状体间接输出通路或纹状体能终末的纹状体腺苷A（2A）受体。这些结果可能与我们了解腺苷A（2A）受体拮抗剂在帕金森病中的作用机制有关。(C)2003 Elsevier Science B. V.保留所有权利。
The objective of the work was to study, by in vivo microdialysis, the effect of the adenosine A(2A) receptor antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261) on glutamate outflow in the striata of unilateral 6-hydroxydopamine-infused rats. Two vertical microdialysis probes were implanted bilaterally in both the denervated striatum and in the intact striatum. Glutamate concentrations in the dialysate were determined by high-performance liquid chromatography (HPLC). Infusion of the adenosine A(2A) receptor antagonist SCH 58261 (50 nM), through the microdialysis fiber, significantly increased glutamate outflow from the denervated striatum while it decreased glutamate outflow from the intact striatum. The opposite effects of SCH 58261 on glutamate outflow in the intact and 6-hydroxydopamine-lesioned striatum might be attributed to blockade of striatal adenosine A(2A) receptors located on either striatal indirect output pathways or glutamatergic terminals. These results may be relevant to our understanding of the mechanism of action of adenosine A(2A) receptor antagonists in Parkinson's disease. (C) 2003 Elsevier Science B.V. All rights reserved.