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KMID : 0356920080550060716
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Korean Journal of Anesthesiology
2008 Volume.55 No. 6 p.716 ~ p.722
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Cardioprotective signaling cascade of A2 adenosine receptor agonist 5’-N-ethylcarboxaminidoadenosine against myocardial reperfusion injury
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Lee Yong-Cheol
Kim Jin-Mo
Jang Young-Ho
Kim Chan-Jin
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Abstract
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Background: This experiments investigated the signaling cascade responsible for anti-infarct effect by an A2 adenosine receptor (AR) agonist 5’-N-Ethylcarboxaminidoadenosine (NECA).
Methods: Langendorff perfused isolated rat hearts were subjected to 30 minutes of regional ischemia and 120 minutes of reperfusion. Drugs were perfused for a period of 5 minutes before and 60 minutes after reperfusion. For comparison of cardioprotection among groups, area at necrosis (AN) and area at risk (AAR) were measured by triphenyltetrazolium chloride staining.
Results: NECA significantly attenuated AN/AAR (14.1 ± 1.9%, P ＜ 0.001) compared with control hearts (30.7 ± 2.8%). Anti-infarct effect by NECA was attenuated by an A2AAR antagonist 8-(3-chlorostyryl)caffeine (23.7 ± 3.4%, P ＜ 0.05) and an A2BAR antagonist MRS1706 (29.9 ± 3.3%, P ＜ 0.001). Cardioprotection by NECA was blocked by a guanylyl cyclase inhibitor (23.1 ± 2.9%, P ＜ 0.05) and a protein kinase G (PKG) inhibitor KT5823 (30.3 ± 3.2%, P ＜ 0.001). Glycogen synthase kinase-3? (GSK-3?) inhibitor SB216763 attenuated the AN/AAR in both NECA with MRS (17.8 ± 2.7%, P ＜ 0.01 vs. control) and NECA with KT5823 treated hearts (8.2 ± 1.8%, P ＜ 0.001 vs. control). The mitochondrial permeability transition pore (mPTP) opener atractyloside also aborted NECA’s anti-infarct effect (24.7 ± 2.4% P ＜ 0.05).
b>Conclusions: The signaling pathway by NECA administered at reperfusion involves the activation of both A2AAR
and A2BAR and cGMP/PKG pathway, which in turn depends on inactivation of GSK-3? and inhibition of mPTP opening.
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KEYWORD
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adenosine receptor, mitochondria, myocardial infarction, NECA, reperfusion injury
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