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中枢神经系统中的嘌呤受体。

Purinoceptors in the Central Nervous System.

作者信息

Dunwiddie T V, Abbracchio M P, Bischofberger N, Brundege J M, Buell G, Collo G, Corsi C, Diao L, Kawashima E, Jacobson K A, Latini S, Lin R C S, North R A, Pazzagli M, Pedata F, Pepeu G C, Proctor W R, Rassendren F, Surprenant A, Cattabeni F

出版信息

Drug Dev Res. 1996 Nov-Dec;39(3-4):361-370. doi: 10.1002/(sici)1098-2299(199611/12)39:3/4<361::aid-ddr17>3.0.co;2-4.

Abstract

New exciting developments on the occurrence and functional role of purinoceptors in mammalian brain were presented at the session "Purinoceptors in the central nervous system" chaired by Flaminio Cattabeni and Tom Dunwiddie at the Purines '96 international conference. The focus of the session were topics of recent interest, including the sources and mechanisms involved in ATP and adenosine release during physiological neurotransmission in hippocampus, the brain expression of the recently cloned P2 receptors, and the role of the various adenosine receptor subtypes in brain protection from neurodegeneration associated with trauma-, ischemia-and excessive excitatory amino acid neurotransmission. New important insights into the mechanisms responsible for the formation and release of adenosine into the extracellular space were provided by data obtained by Dunwiddie and coworkers in hippocampal pyramidal neurons. These data may have functional implications for the role of purines in modulation of synaptic plasticity and long-term potentiation in this brain area, and hence in cognitive functions. Buell provided an updated overview on the cloning, molecular characteristics and brain expression of various ligand-gated P2X purinoceptors; although the functional role of these receptors in mammalian brain still awaits elucidation, their widespread distribution in the nervous system strongly suggests that ATP-mediated events are more prevalent and important in brain than expected. Pedata presented data on the functional interrelationships between adenosine and glutamate in the brain, and also provided evidence for alterations of the reciprocal regulation between these two systems in aged brain, which may have important implications for both ischemia-and trauma-associated neurodegenerative events and senescence-associated cognitive impairment. Finally, von Lubitz provided novel data on the molecular mechanisms likely to be at the basis of the brain protective effects associated with the chronic stimulation of the adenosine A receptor, further confirming that this receptor represents a crucial target for the development of new antiischemic and antineurodegenerative therapeutic agents.

摘要

在由弗拉米尼奥·卡塔贝尼和汤姆·邓威迪主持的“中枢神经系统中的嘌呤受体”会议上,展示了哺乳动物大脑中嘌呤受体的发生及功能作用方面令人兴奋的新进展。该会议是在嘌呤96国际会议期间举行的。会议重点关注了近期感兴趣的话题,包括海马体生理神经传递过程中ATP和腺苷释放的来源及机制、最近克隆的P2受体在大脑中的表达,以及各种腺苷受体亚型在保护大脑免受与创伤、缺血和过度兴奋性氨基酸神经传递相关的神经退行性变中的作用。邓威迪及其同事在海马体锥体细胞中获得的数据,为腺苷形成并释放到细胞外空间的机制提供了新的重要见解。这些数据可能对嘌呤在调节该脑区突触可塑性和长时程增强作用中的作用具有功能意义,进而对认知功能也有意义。比尔提供了关于各种配体门控P2X嘌呤受体的克隆、分子特征及大脑表达的最新综述;尽管这些受体在哺乳动物大脑中的功能作用仍有待阐明,但它们在神经系统中的广泛分布强烈表明,ATP介导的事件在大脑中比预期更为普遍和重要。佩达塔展示了大脑中腺苷和谷氨酸之间功能相互关系的数据,还提供了证据表明在老年大脑中这两个系统之间的相互调节发生了改变,这可能对与缺血和创伤相关的神经退行性事件以及与衰老相关的认知障碍都具有重要意义。最后,冯·卢比茨提供了关于可能是腺苷A受体慢性刺激相关脑保护作用基础的分子机制的新数据,进一步证实该受体是开发新的抗缺血和抗神经退行性治疗药物的关键靶点。

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