Both A2a and A2b adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts
Both A2a and A2b adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts
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DOI：
10.1152/ajpheart.00181.2010
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发表时间：
2010-10-01
影响因子：
4.8
通讯作者：
Krieg, Thomas
中科院分区：
文献类型：
--
作者：
Methner, Carmen;Schmidt, Katharina;Krieg, Thomas
Methner C, Schmidt K, Cohen MV, Downey JM, Krieg T. A（2a）和A（2b）腺苷受体在小鼠心脏再灌注中的作用。[J]中国生物医学工程学报，2010,31(2):444 - 444。首次发表于2010年8月13日；doi: 10.1152 / ajpheart.00181.2010。预适应和后适应依赖于缺血指数结束时腺苷受体（ARs）的激活。这项研究的目的是确定哪些受体亚型必须被激活。小鼠原位心脏局部缺血30分钟，再灌注2小时。正如预期的那样，缺血后适应（10秒再灌注和10秒冠状动脉闭塞的6个周期）或在再灌注前5分钟开始注射选择性A（2b）腺苷受体（A(2b)AR）激动剂BAY60-6583 (BAY60) 60分钟，均可减少野生型C57Bl/6N小鼠的梗死面积。选择性A(2b)AR拮抗剂MRS-1754消除了对两者的保护作用，证实了A(2b)AR的作用。此外，缺血后适应和选择性a (2a)AR拮抗剂的联合使用也会导致保护作用的丧失。5'-外核苷酶（CD73）被认为是缺血时腺苷生成所必需的。正如预测的那样，缺血后适应不能保护CD73敲除小鼠。A(2b)AR （BAY60）或A(2a)AR （CGS-21680）的选择性激动剂，以及缺血后适应和BAY60的联合给药，也未能保护CD73敲除小鼠的心脏。但非选择性的A(1)/A(2)AR激动剂5'-（n -乙基羧胺）腺苷（NECA）具有保护作用，表明可能需要激活多种AR亚型。CGS-21680和BAY60共同给药也能产生深远的保护作用，这表明必须同时激活两种AR亚型A（2a）和A（2b）才能产生保护作用。
Methner C, Schmidt K, Cohen MV, Downey JM, Krieg T. Both A(2a) and A(2b) adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts. Am J Physiol Heart Circ Physiol 299: H1262-H1264, 2010. First published August 13, 2010; doi:10.1152/ajpheart.00181.2010.-Pre- and postconditioning depend on the activation of adenosine receptors (ARs) at the end of the index ischemia. The aim of this study was to determine which receptor subtypes must be activated. In situ mouse hearts underwent 30 min of regional ischemia, followed by 2 h of reperfusion. As expected, either ischemic postconditioning (6 cycles of 10 s of reperfusion and 10 s of coronary occlusion) or infusion of the selective A(2b) adenosine receptor (A(2b)AR) agonist BAY60-6583 (BAY60) for 60 min, starting 5 min before reperfusion reduced infarct size in wild-type C57Bl/6N mice. Protection from either was abolished by the selective A(2b)AR antagonist MRS-1754, confirming a role for A(2b)AR. Additionally, the coadministration of ischemic postconditioning and a selective A(2a)AR antagonist led to the loss of protection as well. 5'-Ectonucleotidase (CD73) is thought to be necessary for the production of adenosine during ischemia. As predicted, ischemic postconditioning did not protect CD73 knockout mice. Selective agonists of either A(2b)AR (BAY60) or A(2a)AR (CGS-21680), as well as the coadministration of ischemic postconditioning and BAY60, also failed to protect hearts of the CD73 knockout mice. But the nonselective A(1)/A(2)AR agonist 5'-(N-ethylcarboxamido) adenosine (NECA) was protective, suggesting that the activation of multiple AR subtypes might be required. The coadministration of CGS-21680 and BAY60 also elicited profound protection, indicating that two AR subtypes, A(2a) and A(2b), must be simultaneously activated for protection to occur.