乙醇块腺苷通过抑制核苷吸收运输系统在支气管上皮细胞。

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Allen-Gipson DS,贾雷尔JC,贝利KL,罗宾逊我,Kharbanda KK, Sisson JH,怀亚特的助教

乙醇块腺苷通过抑制核苷吸收运输系统在支气管上皮细胞。

酒精实验研究杂志2009;33 (5):791 - 8。doi: 10.1111 / j.1530-0277.2009.00897.x。Epub 2009年3月6日。

PubMed ID

19298329 (在PubMed

]

文摘

背景:腺苷核苷转运蛋白进入细胞的吸收起着重要的作用在调节细胞外腺苷浓度。细胞外腺苷是一种重要的信号分子,调节许多细胞功能通过4 G-protein-coupled受体亚型((1)、(2)、一(2 b),和(3))。以前,我们表明,腺苷是维持气道内稳态的关键和气道修复和气道宿主防御被酒精受损。综上所述,我们假设乙醇损害腺苷通过核苷吸收交通系统。方法:检查ethanol-induced变更腺苷交通,我们使用了一个人类支气管上皮细胞系(BEAS-2B)。细胞被preincubated 10分钟的存在和缺乏不同浓度的乙醇(EtOH)。此外,一些细胞使用S - (4-Nitrobenzyl) 6-thioinosine (100 microM:电视台),一个强有力的腺苷酸吸收抑制剂。吸收是由添加[(3)H]腺苷在不同的时间间隔。结果:增加EtOH导致浓度增加抑制腺苷吸收测量时1分钟。用电视台有效地阻止腺苷预处理细胞吸收。 In addition, short-term EtOH revealed increased extracellular adenosine concentration. Conversely, adenosine transport became desensitized in cells exposed to EtOH (100 mM) for 24 hours. To determine the mechanism of EtOH-induced desensitization of adenosine transport, cAMP activity was assessed in response to EtOH. Short-term EtOH exposure (10 minutes) had little or no effect on adenosine-mediated cAMP activation, whereas long-term EtOH exposure (24 hours) blocked adenosine-mediated cAMP activation. Western blot analysis of lysates from unstimulated BEAS-2B cells detected a single 55 kDa band indicating the presence of hENT1 and hENT2, respectively. Real-time RT-PCR of RNA from BEAS-2B revealed transcriptional expression of ENT1 and ENT2. CONCLUSIONS: Collectively, these data reveal that acute exposure of cells to EtOH inhibits adenosine uptake via a nucleoside transporter, and chronic exposure of cells to EtOH desensitizes the adenosine transporter to these inhibitory effects of ethanol. Furthermore, our data suggest that inhibition of adenosine uptake by EtOH leads to an increased extracellular adenosine accumulation, influencing the effect of adenosine at the epithelial cell surface, which may alter airway homeostasis.

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药物靶点

药物	目标	类	生物	药理作用	行动
乙醇	Equilibrative核苷转运体1	蛋白质	人类	未知的	不可用	细节
乙醇	Equilibrative核苷转运蛋白2	蛋白质	人类	未知的	不可用	细节