离子通道型嘌呤受体P2X4在中枢神经系统中的作用及其作为神经系统疾病干预靶标的前景

摘要

Adenosine 5-triphosphate is not only the source of cellular energy,but also the extracel-lular signal molecule that binds two different classes of ATP receptors:ionotropic P2X receptors and G-protein-coupled P2Y receptors.P2X4 receptor is one of the ionotropic P2X receptors widely expressed in the central nervous system(CNS).This subtype of the ionotropic P2X receptor is implicated in many physiological and pathological functions in the CNS, including chronic pain, alcohol abuse, seizures, Alzheimer′s and Parkinson′s diseases,and stroke.Therefore,P2X4 receptor has attracted attention as a promising drug target.Here,we review the findings of research or the physiological and pathological functions of P2X4 in the CNS. Recent progress in the development of new pharmacological agents of P2X4,such as selective antagonists,is also presented here.%ATP除了作为细胞内能量来源物质,也可充当细胞外信号分子激活离子通道型的嘌呤受体P2X受体和G蛋白偶联受体型的P2Y受体.P2X4亚型是一类在中枢神经系统(CNS)广泛表达的P2X受体,通过感受胞外ATP的刺激而参与CNS生理过程,包括慢性痛、乙醇滥用、癫痫、阿尔茨海默病、帕金森病和卒中缺血等.因此,靶向P2X4受体的小分子拮抗剂或增强剂因为其药用前景而受到广泛关注.本文总结了P2X4受体在CNS中相关研究的进展情况,概述了近年来新发现的P2X4受体高选择性拮抗剂.