Cardioprotective signaling cascade of A2 adenosine receptor agonist 5'-N-ethylcarboxaminidoadenosine against myocardial reperfusion injury.
10.4097/kjae.2008.55.6.716
- Author:
Yong Cheol LEE
1
;
Young Ho JANG
;
Chan Jin KIM
;
Jin Mo KIM
Author Information
1. Department of Anesthesiology and Pain Medicine, School of Medicine, Keimyung University, Daegu, Korea.
- Publication Type:Original Article
- Keywords:
adenosine receptor;
mitochondria;
myocardial infarction;
NECA;
reperfusion injury
- MeSH:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine;
Adenosine;
Adenosine-5'-(N-ethylcarboxamide);
Animals;
Atractyloside;
Caffeine;
Carbazoles;
Cyclic GMP-Dependent Protein Kinases;
Glycogen Synthase;
Glycogen Synthase Kinase 3;
Guanylate Cyclase;
Heart;
Indoles;
Ischemia;
Maleimides;
Mitochondria;
Mitochondrial Membrane Transport Proteins;
Myocardial Infarction;
Myocardial Reperfusion;
Myocardial Reperfusion Injury;
Necrosis;
Permeability;
Purines;
Rats;
Receptors, Purinergic P1;
Reperfusion;
Reperfusion Injury;
Tetrazolium Salts
- From:Korean Journal of Anesthesiology
2008;55(6):716-722
- CountryRepublic of Korea
- Language:Korean
-
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 A(2A)AR antagonist 8-(3-chlorostyryl)caffeine (23.7 +/- 3.4%, P < 0.05) and an A(2B)AR 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-3beta (GSK-3beta) 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-3beta and inhibition of mPTP opening.
