Adenosine receptors co-operate with NMDA preconditioning to protect cerebellar granule cells against glutamate neurotoxicity
Adenosine receptors co-operate with NMDA preconditioning to protect cerebellar granule cells against glutamate neurotoxicity
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DOI：
10.1016/j.neuropharm.2005.01.024
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发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Vendite, D
中科院分区：
文献类型：
--
作者：
Boeck, CR;Kroth, EH;Vendite, D
N-甲基-D-天冬氨酸（NMDA）预处理诱发亚毒性浓度的NMDA（50 μ M），这已被证明导致短暂的抵抗随后致死剂量的谷氨酸或NMDA在培养的神经元。本研究旨在探讨腺苷A（1）和A（2A）受体参与NMDA预处理对抗谷氨酸诱导的小脑颗粒细胞损伤。NMDA预处理可抑制谷氨酸对AMP水解的刺激作用，但对ADP水解无影响。腺苷A（2A）受体拮抗剂8-环戊基-1，3-二甲基黄嘌呤（8-cyclopentyl-1，3-dimethylxanthine）可阻断NMDA预处理对谷氨酸诱导的细胞损伤的保护作用（CPT，100 nM），但不被腺苷A（2A）受体拮抗剂，（4-（2[7-氨基-2-（2-呋喃基{1，2，4}-三唑并{2，3-a{1，3，5}三嗪-5-基-氨基乙基）苯酚（ZM 241385，50 nM）。有趣的是，单独用CPT或ZM 241385长期处理保护细胞免受谷氨酸诱导的神经毒性。此外，腺苷A（2A）受体的功能不受NMDA预处理的影响，但这种处理促进腺苷A（2A）受体脱敏，测量cAMP的积累。总而言之，本文所述的结果表明，针对谷氨酸引起的细胞损伤，NMDA预处理引起的神经保护作用是通过涉及腺苷A（2A）受体脱敏与小脑颗粒细胞中腺苷A（1）受体激活协同作用的机制发生的。(c)2005爱思唯尔有限公司保留所有权利。
N-Methyl-D-aspartate (NMDA) preconditioning is evoked by subtoxic concentrations of NMDA (50 mu M), which has been shown previously to lead to transient resistance to subsequent lethal dose of glutamate or NMDA in cultured neurons. The purpose of this study was to investigate the participation of adenosine A(1) and A(2A) receptors on NMDA preconditioning against glutamate-induced cellular damage in cerebellar granule cells. NMDA preconditioning prevented the stimulatory effect induced by glutamate on AMP hydrolysis, but not on ADP hydrolysis. The neuroprotection evoked by NMDA preconditioning against glutamate-induced cellular damage was prevented by the presence of adenosine A(2A) receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT, 100 nM), but not by the adenosine A(2A) receptors antagonist, (4-(2[7-amino-2-(2-furyl {1,2,4}-triazolo{2,3-a{1,3,5}triazian-5-yl-aminoethyl)phenol (ZM 241385, 50 nM). Interestingly, a long-term treatment with CPT or ZM 241385 alone protected cells against glutamate-induced neurotoxicity. Moreover, the functionality of adenosine A(2A) receptor was not affected by NMDA preconditioning, but this treatment promoted adenosine A(2A) receptor desensitization, measured by cAMP accumulation. Taken together, the results described herein suggest that the neuroprotection evoked by NMDA preconditioning against cellular damage elicited by glutamate occurs through mechanisms involving adenosine A(2A) receptors desensitization co-operating with adenosine A(1) receptors activation in cerebellar granule cells. (c) 2005 Elsevier Ltd. All rights reserved.