Adenosine A1-A2A receptor heteromers:: new targets for caffeine in the brain
Adenosine A1-A2A receptor heteromers:: new targets for caffeine in the brain
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DOI：
10.2741/2852
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Goldberg, Steven R.
中科院分区：
文献类型：
--
作者：
Ferre, Sergi;Ciruela, Francisco;Goldberg, Steven R.
腺苷A(1)和A(2A)受体的阻断在咖啡因的精神刺激作用中的作用仍然存在争议。当分析大鼠的运动活动时，急性给予咖啡因显示出非选择性腺苷受体拮抗剂的特征，尽管具有优先的A(1)受体拮抗剂。另一方面，对A(1)受体阻滞剂的耐受性似乎主要是对咖啡因的运动激活效应的耐受性，而咖啡因在耐受者身上残留的运动激活效应似乎涉及A(2A)受体阻滞剂。这些行为研究与体内微透析实验相关联，这些实验表明A(1)受体介导的纹状体谷氨酸释放的调节参与了咖啡因的精神刺激作用。在转基因细胞中的实验证明了A(1)受体与A(2A)受体异构化的能力，并且A(1)-A(2A)受体异构体可以在纹状体的谷氨酸能终末进行生化鉴定。纹状体A(1)-A(2A)受体异构体提供了一种“浓度依赖开关”机制，通过这种机制，低浓度和高浓度突触腺苷对谷氨酸的释放产生相反的影响。对A(1)-A(2A)受体异构体在咖啡因慢性治疗过程中的作用的分析，为人们对咖啡因的精神刺激作用耐受这一众所周知的现象提供了新的线索。
The contribution of blockade of adenosine A(1) and A(2A) receptor to the psychostimulant effects of caffeine is still a matter of debate. When analyzing motor activity in rats, acutely administered caffeine shows a profile of a nonselective adenosine receptor antagonist, although with preferential A(1) receptor antagonism. On the other hand, tolerance to the effects of A(1) receptor blockade seems to be mostly responsible for the tolerance to the motor-activating effects of caffeine, while the residual motor-activating effects of caffeine in tolerant individuals seem to involve A(2A) receptor blockade. These behavioral studies correlate with in vivo microdialysis experiments that suggest that A(1) receptor-mediated modulation of striatal glutamate release is involved in the psychostimulant effects of caffeine. Experiments in transfected cells demonstrate the ability of A(1) receptors to heteromerize with A(2A) receptors and the A(1)-A(2A) receptor heteromer can be biochemically identified in the striatum, in striatal glutamatergic terminals. The striatal A(1)-A(2A) receptor heteromer provides a "concentration-dependent switch" mechanism by which low and high concentrations of synaptic adenosine produce the opposite effects on glutamate release. The analysis of the function of A(1)-A(2A) receptor heteromers during chronic treatment with caffeine gives new clues about the well-known phenomenon of tolerance to the psychostimulant effects of caffeine.