Kato Fusao, Kawamura Masahito, Shigetomi Eiji, Tanaka Jun-Ichi, Inoue Kazuhide
Laboratory of Neurophysiology, Department of Neuroscience, Jikei University School of Medicine, Tokyo, Japan.
J Pharmacol Sci. 2004 Feb;94(2):107-11. doi: 10.1254/jphs.94.107.
The studies aiming to understand the function of purinoceptors in the central nervous system (CNS), which has been explored mostly in isolated and cultured cell systems, are now at the stage of identifying their physiological and pathophysiological significance in the native organs, tissues, and whole animals. The results of our recent studies made in brain slice preparations are not in full accordance with what have been demonstrated in isolated cells, mostly due to strong interplay between ATP receptors, adenosine receptors, and ecto-nucleotidases. This suggests that these proteins form coordinated regulation systems in the native tissue, controlling the local network behaviors through regulating the balance between the effects of ATP and adenosine on synaptic transmissions. We propose that this tripartite regulation system by extracellular purines may be an important target of CNS drugs.
旨在了解嘌呤受体在中枢神经系统(CNS)中功能的研究,此前大多在分离和培养的细胞系统中进行探索,目前正处于确定其在天然器官、组织和整个动物体内生理和病理生理意义的阶段。我们最近在脑片制备中进行的研究结果与在分离细胞中所证明的结果并不完全一致,这主要是由于ATP受体、腺苷受体和胞外核苷酸酶之间存在强烈的相互作用。这表明这些蛋白质在天然组织中形成了协调的调节系统,通过调节ATP和腺苷对突触传递的作用之间的平衡来控制局部网络行为。我们提出,这种由细胞外嘌呤构成的三方调节系统可能是中枢神经系统药物的一个重要靶点。