Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury
Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury
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DOI：
10.1096/fj.13-228551
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发表时间：
2013-08-01
期刊：
影响因子：
4.8
通讯作者：
Eltzschig, Holger K.
中科院分区：
文献类型：
--
作者：
Eckle, Tobias;Hughes, Kelly;Eltzschig, Holger K.
信号分子腺苷已被牵连在减轻急性肺损伤（ALI）。腺苷信号传导通过其通过平衡核苷转运体（ENT）的摄取而终止。我们假设ENT依赖的腺苷摄取可以靶向增强腺苷介导的肺保护作用。为了解决这个假设，我们将小鼠暴露于高压机械通气以诱导ALI。初步研究表明，ALI期间ENT 1和ENT 2转录和蛋白水平的时间依赖性抑制。为了研究ENT抑制代表内源性适应性反应的论点，我们用ENT抑制剂潘生丁进行了功能研究。双嘧达莫治疗（1 mg/kg; EC 50 =10 M）与ALI存活时间显著增加相关（277 vs. 395 min; P
The signaling molecule adenosine has been implicated in attenuating acute lung injury (ALI). Adenosine signaling is terminated by its uptake through equilibrative nucleoside transporters (ENTs). We hypothesized that ENT-dependent adenosine uptake could be targeted to enhance adenosine-mediated lung protection. To address this hypothesis, we exposed mice to high-pressure mechanical ventilation to induce ALI. Initial studies demonstrated time-dependent repression of ENT1 and ENT2 transcript and protein levels during ALI. To examine the contention that ENT repression represents an endogenous adaptive response, we performed functional studies with the ENT inhibitor dipyridamole. Dipyridamole treatment (1 mg/kg; EC50=10 M) was associated with significant increases in ALI survival time (277 vs. 395 min; P