Schwiebert Erik M, Zsembery Akos
Department of Physiology and Biophysics, University of Alabama at Birmingham, 35294-0005, USA.
Biochim Biophys Acta. 2003 Sep 2;1615(1-2):7-32. doi: 10.1016/s0005-2736(03)00210-4.
The charge of this invited review is to present a convincing case for the fact that cells release their ATP for physiological reasons. Many of our "purinergic" colleagues as well as ourselves have experienced resistance to this concept, because it is teleologically counter-intuitive. This review serves to integrate the three main tenets of extracellular ATP signaling: ATP release from cells, ATP receptors on cells, and ATP receptor-driven signaling within cells to affect cell or tissue physiology. First principles will be discussed in the Introduction concerning extracellular ATP signaling. All possible cellular mechanisms of ATP release will then be presented. Use of nucleotide and nucleoside scavengers as well as broad-specificity purinergic receptor antagonists will be presented as a method of detecting endogenous ATP release affecting a biological endpoint. Innovative methods of detecting released ATP by adapting luciferase detection reagents or by using "biosensors" will be presented. Because our laboratory has been primarily interested in epithelial cell physiology and pathophysiology for several years, the role of extracellular ATP in regulation of epithelial cell function will be the focus of this review. For ATP release to be physiologically relevant, receptors for ATP are required at the cell surface. The families of P2Y G protein-coupled receptors and ATP-gated P2X receptor channels will be introduced. Particular attention will be paid to P2X receptor channels that mediate the fast actions of extracellular ATP signaling, much like neurotransmitter-gated channels versus metabotropic heptahelical neurotransmitter receptors that couple to G proteins. Finally, fascinating biological paradigms in which extracellular ATP signaling has been implicated will be highlighted. It is the goal of this review to convert and attract new scientists into the exploding field of extracellular nucleotide signaling and to convince the reader that extracellular ATP is indeed a signaling molecule.
这篇特邀综述的任务是，为细胞出于生理原因释放ATP这一事实提供有说服力的证据。我们许多“嘌呤能”领域的同行以及我们自己都曾遇到过对这一概念的抵触，因为从目的论角度来看它有违直觉。这篇综述旨在整合细胞外ATP信号传导的三个主要原则：细胞释放ATP、细胞上的ATP受体以及细胞内由ATP受体驱动的信号传导，以影响细胞或组织的生理功能。引言部分将讨论细胞外ATP信号传导的基本原理。随后将介绍ATP释放的所有可能细胞机制。将介绍使用核苷酸和核苷清除剂以及广泛特异性嘌呤能受体拮抗剂作为检测影响生物学终点的内源性ATP释放的方法。还将介绍通过改造荧光素酶检测试剂或使用“生物传感器”来检测释放的ATP的创新方法。由于我们实验室多年来主要关注上皮细胞的生理学和病理生理学，因此细胞外ATP在调节上皮细胞功能中的作用将是本综述的重点。为使ATP释放具有生理相关性，细胞表面需要有ATP受体。将介绍P2Y G蛋白偶联受体家族和ATP门控P2X受体通道。将特别关注介导细胞外ATP信号快速作用的P2X受体通道，这很像神经递质门控通道与偶联G蛋白的代谢型七螺旋神经递质受体的对比。最后，将突出介绍涉及细胞外ATP信号传导的引人入胜的生物学范例。本综述的目的是吸引新科学家进入细胞外核苷酸信号传导这一蓬勃发展领域，并使读者相信细胞外ATP确实是一种信号分子。
