Targeting the A2B adenosine receptor during gastrointestinal ischemia and inflammation.
Targeting the A2B adenosine receptor during gastrointestinal ischemia and inflammation.
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DOI：
10.1517/14728220903241666
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发表时间：
2009-11
影响因子：
5.8
通讯作者：
Colgan SP
中科院分区：
文献类型：
--
作者：
Eltzschig HK;Rivera-Nieves J;Colgan SP
细胞外腺苷通过激活四种不同的腺苷受体（A1、A2A、A2B 和 A3）作为内源性求救信号发挥作用。氧气供应有限或急性炎症会导致细胞外腺苷水平升高并增强信号传导事件。这与四种机制的组合有关：i) 通过前体分子（特别是 ATP 和 ADP）的细胞外磷酸水解增加腺苷的产生； ii) 通过缺氧诱导的腺苷受体，特别是 A2B 腺苷受体，表达和信号传导增加； iii) 从细胞外向细胞内区室的摄取减弱； iv) 细胞内代谢减弱。由于其表面积大，粘膜器官特别容易发生缺氧和缺血相关的炎症。因此，腺苷的产生和信号传导在减轻肠道缺血或炎症期间的组织炎症和损伤方面发挥核心作用也就不足为奇了。事实上，最近结合药理学和遗传学方法的研究表明，通过 A2B 腺苷受体的腺苷信号传导可抑制肠道缺血或实验性结肠炎期间的粘膜炎症和组织损伤。本综述概述了细胞外腺苷产生、信号传导、摄取和代谢的基本原理。此外，我们还讨论了该途径在抑制缺氧引起的炎症中的作用，特别是在肠道缺血和炎症的情况下。
Extracellular adenosine functions as an endogenous distress signal via activation of four distinct adenosine receptors (A1, A2A, A2B and A3). Conditions of limited oxygen availability or acute inflammation lead to elevated levels of extracellular adenosine and enhanced signaling events. This relates to a combination of four mechanisms: i) increased production of adenosine via extracellular phosphohydrolysis of precursor molecules (particularly ATP and ADP); ii) increased expression and signaling via hypoxia-induced adenosine receptors, particularly the A2B adenosine receptor; iii) attenuated uptake from the extracellular towards the intracellular compartment; and iv) attenuated intracellular metabolism. Due to their large surface area, mucosal organs are particularly prone to hypoxia and ischemia associated inflammation. Therefore, it is not surprising that adenosine production and signaling plays a central role in attenuating tissue inflammation and injury during intestinal ischemia or inflammation. In fact, recent studies combining pharmacological and genetic approaches demonstrated that adenosine signaling via the A2B adenosine receptor dampens mucosal inflammation and tissue injury during intestinal ischemia or experimental colitis. This review outlines basic principles of extracellular adenosine production, signaling, uptake and metabolism. In addition, we discuss the role of this pathway in dampening hypoxia-elicited inflammation, specifically in the setting of intestinal ischemia and inflammation.
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影响因子：
3.7
作者：
Faigle, Marion;Seessle, Jessica;Zug, Stephanie;El Kasmi, Karim C.;Eltzschig, Holger K.
通讯作者：
Eltzschig, Holger K.
影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
影响因子：
29.4
作者：
Collins, Colm B.;Ho, Johnson;Rivera-Nieves, Jesus
通讯作者：
Rivera-Nieves, Jesus
影响因子：
20.1
作者：
Casanello, P;Torres, A;Sobrevia, L
通讯作者：
Sobrevia, L
影响因子：
20.3
作者：
Eltzschig, HK;Thompson, LF;Colgan, SP
通讯作者：
Colgan, SP