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A2 Adenosine 작용약물인 5’-N-Ethylcarboxaminidoadenosine의 심근 재관류 손상에 대한 심장 보호 기전

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Author(s)
이용철장영호김찬진김진모
Keimyung Author(s)
Lee, Yong CheolKim, Jin Mo
Department
Dept. of Anesthesiology & Pain Medicine (마취통증의학)
Journal Title
Korean Journal of Anesthesiology
Issued Date
2008
Volume
55
Issue
6
Abstract
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-3β
(GSK-3β) 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).
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-3β and inhibition of mPTP opening. (Korean J Anesthesiol
2008; 55: 716~22)
Alternative Title
Cardioprotective signaling cascade of A2 adenosine receptor agonist 5’-N-ethylcarboxaminidoadenosine against myocardial reperfusion injury
Keimyung Author(s)(Kor)
이용철
김진모
Publisher
School of Medicine
Citation
이용철 et al. (2008). A2 Adenosine 작용약물인 5’-N-Ethylcarboxaminidoadenosine의 심근 재관류 손상에 대한 심장 보호 기전. Korean Journal of Anesthesiology, 55(6), 716–722. doi: 10.4097/kjae.2008.55.6.716
Type
Article
ISSN
2005-6419
DOI
10.4097/kjae.2008.55.6.716
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/38508
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Anesthesiology & Pain Medicine (마취통증의학)
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