Dubyak G R, el-Moatassim C
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Am J Physiol. 1993 Sep;265(3 Pt 1):C577-606. doi: 10.1152/ajpcell.1993.265.3.C577.
Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5'-nucleotidases. The diverse biological responses to ATP are mediated by a variety of cell surface receptors that are activated when ATP or other nucleotides are bound. The functionally identified nucleotide or P2-purinergic receptors include 1) ATP receptors that stimulate G protein-coupled effector enzymes and signaling cascades, including inositol phospholipid hydrolysis and the mobilization of intracellular Ca2+ stores; 2) ATP receptors that directly activate ligand-gated cation channels in the plasma membranes of many excitable cell types; 3) ATP receptors that, via the rapid induction of surface membrane channels and/or pores permeable to ions and endogenous metabolites, produce cytotoxic or activation responses in macrophages and other immune effector cells; and 4) ADP receptors that trigger rapid ion fluxes and aggregation responses in platelets. Current research in this area is directed toward the identification and structural characterization of these receptors by biochemical and molecular biological approaches.
微摩尔浓度的细胞外ATP可在多种细胞和组织中诱导显著的功能变化。ATP可从受损细胞的胞质溶胶中释放，或从许多类型分泌细胞中含有的胞吐小泡和/或颗粒中释放。对于释放的核苷酸，也存在由胞外ATP酶和5'-核苷酸酶介导的高效细胞外代谢机制。对ATP的多种生物学反应是由多种细胞表面受体介导的，当ATP或其他核苷酸结合时这些受体被激活。功能上已确定的核苷酸或P2-嘌呤能受体包括：1）刺激G蛋白偶联效应酶和信号级联反应的ATP受体，包括肌醇磷脂水解和细胞内Ca2+储备的动员；2）直接激活许多可兴奋细胞类型质膜中配体门控阳离子通道的ATP受体；3）通过快速诱导对离子和内源性代谢物通透的表面膜通道和/或孔，在巨噬细胞和其他免疫效应细胞中产生细胞毒性或激活反应的ATP受体；4）在血小板中触发快速离子通量和聚集反应的ADP受体。该领域目前的研究方向是通过生化和分子生物学方法对这些受体进行鉴定和结构表征。
