Adenosine A2A and A2B receptors work in concert to induce a strong protection against reperfusion injury in rat hearts.
Adenosine A2A and A2B receptors work in concert to induce a strong protection against reperfusion injury in rat hearts.
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DOI：
10.1016/j.yjmcc.2009.08.009
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发表时间：
2009-11
影响因子：
5
通讯作者：
Xu, Zhelong
中科院分区：
文献类型：
--
作者：
Xi, Jinkun;McIntosh, Rachel;Shen, Xiangjun;Lee, SungRyul;Chanoit, Guillaume;Criswell, Hugh;Zvara, David A.;Xu, Zhelong
我们的目的是测试是否需要腺苷A2 A和A2 B受体的刺激来产生有效的心脏保护作用以对抗再灌注损伤。离体大鼠心脏进行30分钟的区域缺血，然后2小时的再灌注。在再灌注时给予腺苷A1/A2受体激动剂5′-（N-乙基甲酰氨基）腺苷（NECA）可减少梗死面积，腺苷A2 A拮抗剂SCH 58261和A2 B拮抗剂MRS 1706均可逆转该作用。A2 B激动剂BAY 60-6583而非选择性A2 A激动剂CGS 21680可减少梗死面积。有趣的是，BAY 60-6583和CGS 21680的组合进一步减小了梗死面积。这些结果表明，A2 A和A2 B受体参与NECA在再灌注时的抗梗死作用。NECA在再灌注时减弱线粒体肿胀，并且这被SCH 58261和MRS 1706阻断，表明NECA激活A2受体可以调节再灌注诱导的线粒体通透性转换孔（mPTP）开放。作为支持，NECA还通过两种A2受体防止心肌细胞中氧化剂诱导的线粒体膜电位（Δ Km）损失和基质Ca 2+过载。此外，NECA在再灌注时增加线粒体糖原合成酶激酶3β（GSK-3β）磷酸化，并且这再次被SCH 58261和MRS 1706阻断。总之，A2 A和A2 B受体协同工作，以防止用NECA处理的大鼠心脏的再灌注损伤。NECA可能通过使线粒体GSK-3β失活而调节mPTP开放，从而保护心脏。需要在再灌注时同时刺激A2 A和A2 B受体才能对再灌注损伤产生强有力的心脏保护作用。
We aimed to test if stimulation of both adenosine A2A and A2B receptors is required to produce an effective cardioprotection against reperfusion injury. Isolated rat hearts were subjected to 30 min regional ischemia followed by 2 h of reperfusion. The adenosine A1/A2 receptor agonist 5′-(N-ethylcarboxamido) adenosine (NECA) given at reperfusion reduced infarct size, an effect that was reversed by both the adenosine A2A antagonist SCH58261 and the A2B antagonist MRS1706. The A2B agonist BAY 60-6583 but not the selective A2A agonist CGS21680 reduced infarct size. Interestingly, a combination of BAY 60-6583 and CGS21680 further reduced infarct size. These results suggest that both A2A and A2B receptors are involved in NECA’s anti-infarct effect at reperfusion. NECA attenuated mitochondrial swelling upon reperfusion and this was blocked by both SCH58261 and MRS1706, indicating that activation of A2 receptors with NECA can modulate reperfusion-induced mitochondrial permeability transition pore (mPTP) opening. In support, NECA also prevented oxidant-induced loss of mitochondrial membrane potential (ΔΨm) and matrix Ca2+ overload in cardiomyocytes via both the A2 receptors. In addition, NECA increased mitochondrial glycogen synthase kinase 3β (GSK-3β) phosphorylation upon reperfusion and this was again blocked by SCH58261 and MRS1706. In conclusion, A2A and A2B receptors work in concert to prevent reperfusion injury in rat hearts treated with NECA. NECA may protect the heart by modulating the mPTP opening through inactivating mitochondrial GSK-3β. A simultaneous stimulation of A2A and A2B receptors at reperfusion is required to produce a strong cardioprotection against reperfusion injury.
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DOI：
10.1152/ajpheart.495.2008
发表时间：
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影响因子：
4.8
作者：
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影响因子：
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作者：
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DOI：
10.1152/ajpheart.00092.2008
发表时间：
2008-11-01
影响因子：
4.8
作者：
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N6-(3-碘苄基)-腺苷-5′-N-甲基甲酰胺通过糖原合酶激酶 3β 抑制线粒体通透性转换孔开放，从而在再灌注时提供心脏保护作用
DOI：
10.1124/jpet.106.101477
发表时间：
2006-07-01
影响因子：
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作者：
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通讯作者：
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