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气道上皮细胞P2Y嘌呤受体：从离子转运到免疫功能

郝媛, 高永雄^*

香港中文大学生物医学学院，香港

摘要

水盐的转运调控对呼吸道、生殖系统以及消化道等多个器官系统的整体功能都至关重要。气道上皮的液体分泌就是通过离子转运产生的渗透压所驱动的，而这种腔面方向渗透梯度的决定因素则是氯离子(Cl−)的外向转运。在各类上皮细胞中，多种经典的信号转导级联都与离子运输的调节相关，其中包括两个为人熟知的胞内信号系统：细胞内钙离子浓度([Ca2+]i)的升高，以及环核苷酸，如环腺苷酸(cAMP)合成率的升高。Cl−的分泌主要是通过开放上皮细胞顶膜面Ca2+激活或cAMP激活的Cl−通道。另外基底面Ca2+激活或cAMP激活钾离子(K+)通道的开放同样对离子跨上皮转运的调节起重要作用，会使细胞超极化从而保持顶面Cl−通道开放，并持续释放Cl−。P2Y受体表达于几乎所有极性上皮的顶膜或基底膜面，并调控分泌液体与电解质的运输。人气道上皮细胞中有多种核苷酸受体的表达。细胞外核苷酸，如UTP和ATP，都是能发动钙离子浓度升高的促分泌素。它们从气道上皮细胞释放到胞外，又以自分泌的形式作用于上皮细胞并刺激跨膜离子转运。与此同时，最新研究结果证明在支气管上皮细胞与其它免疫细胞中，P2Y受体还具有分泌炎症因子的功能。

关键词： 嘌呤受体; 上皮细胞; 离子转运; 炎症; 信号

分类号：R332

Purinergic P2Y receptors in airway epithelia: from ion transport to immune functions

Yuan Hao, Wing-hung Ko^*

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China

Abstract

The regulated transport of salt and water is essential to the integrated function of many organ systems, including the respiratory, reproductive, and digestive tracts. Airway epithelial fluid secretion is a passive process that is driven by osmotic forces, which are generated by ion transport. The main determinant of a luminally-directed osmotic gradient is the mucosal transport of chloride ions (Cl−) into the lumen. As with many epithelial cells, a number of classic signal transduction cascades are involved in the regulation of ion transport. There are two well-known intracellular signaling systems: an increase in intracellular Ca2+ concentration ([Ca2+]i) and an increase in the rate of synthesis of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP). Therefore, Cl− secretion is primarily activated via the opening of apical Ca2+- or cAMP-dependent Cl− channels at the apical membrane. The opening of basolateral Ca2+- or cAMP-activated K+ channels, which hyperpolarizes the cell to maintain the driving force for Cl− exit through apical Cl− channels that are constitutively open, is also important in regulating transepithelial ion transport. P2Y receptors are expressed in the apical and/or basolateral membranes of virtually all polarized epithelia to control the transport of fluid and electrolytes. Human airway epithelial cells express multiple nucleotide receptors. Extracellular nucleotides, such as UTP and ATP, are calcium-mobilizing secretagogues. They are released into the extracellular space from airway epithelial cells and act on the same cell in an autocrine fashion to stimulate transepithelial ion transport. In addition, recent data support the role of P2Y receptors in releasing inflammatory cytokines in the bronchial epithelium and other immune cells.

Key words: purinergic receptor; epithelia; ion transport; inflammation; signaling

收稿日期：　　录用日期：

通讯作者：高永雄　　E-mail: whko@cuhk.edu.hk

引用本文：

郝媛, 高永雄. 气道上皮细胞P2Y嘌呤受体：从离子转运到免疫功能[J]. 生理学报 2014; 66 (1): 16-22.

Yuan Hao, Wing-hung Ko. Purinergic P2Y receptors in airway epithelia: from ion transport to immune functions. Acta Physiol Sin 2014; 66 (1): 16-22 (in Chinese with English abstract).