Regulation of K+ current in human airway epithelial cells by exogenous and autocrine adenosine
Regulation of K+ current in human airway epithelial cells by exogenous and autocrine adenosine
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DOI：
10.1152/ajpcell.2001.281.6.c1991
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发表时间：
2001-12-01
影响因子：
5.5
通讯作者：
Duszyk, M
中科院分区：
文献类型：
--
作者：
Szkotak, AJ;Ng, AML;Duszyk, M
腺苷对离子通道功能的调节作用是由四种不同的膜受体介导的。腺苷在这些受体附近的浓度在一定程度上是由向内定向的核苷转运控制的。本研究的目的是研究腺苷对A549细胞离子通道的影响以及核苷转运体在这一调节中的作用。离子置换和药理学研究表明，腺苷和一种人类平衡核苷转运体(Hent)-1的抑制物--硝基苄基硫代肌苷，激活了K+通道，很可能是依赖于钙离子的中间电导K+(I-K)通道。A(1)受体拮抗剂而不是A(2)受体拮抗剂阻断腺苷的作用。RT-PCR结果显示，A549细胞表达I-K-1通道及A(1)、A(2A)和A(2B)受体的mRNA，但不表达A(3)受体。同样，检测到平衡型(hENT1和hENT2)但不集中(hCNT1、hCNT2和hCNT3)核苷转运体的mRNA，这一结果在功能摄取研究中得到了证实。这些研究表明，腺苷控制着A549细胞中K+通道的功能，hENTs在这一过程中起着至关重要的作用。
The regulatory actions of adenosine on ion channel function are mediated by four distinct membrane receptors. The concentration of adenosine in the vicinity of these receptors is controlled, in part, by inwardly directed nucleoside transport. The purpose of this study was to characterize the effects of adenosine on ion channels in A549 cells and the role of nucleoside transporters in this regulation. Ion replacement and pharmacological studies showed that adenosine and an inhibitor of human equilibrative nucleoside transporter (hENT)-1, nitrobenzylthioinosine, activated K+ channels, most likely Ca2+-dependent intermediate-conductance K+ (I-K) channels. A(1) but not A(2) receptor antagonists blocked the effects of adenosine. RT-PCR studies showed that A549 cells expressed mRNA for I-K-1 channels as well as A(1), A(2A), and A(2B) but not A(3) receptors. Similarly, mRNA for equilibrative (hENT1 and hENT2) but not concentrative (hCNT1, hCNT2, and hCNT3) nucleoside transporters was detected, a result confirmed in functional uptake studies. These studies showed that adenosine controls the function of K+ channels in A549 cells and that hENTs play a crucial role in this process.