Document Detail

Adenosine A(3) receptor activation protects the myocardium from reperfusion/reoxygenation injury.
MedLine Citation:
PMID:  12234780     Owner:  NLM     Status:  MEDLINE    
Ischemia-reperfusion induces both necrotic and apoptotic cell death. The ability of adenosine to attenuate reperfusion-induced injury (RI) and the role played by adenosine receptors are unclear. We therefore studied the role of the A(3) receptor (A(3)R) in ameliorating RI using the specific A(3)R agonist 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxi-N-methyl-b-D-ribofuranuronamide (2-Cl-IB-MECA). Isolated rat hearts and cardiomyocytes were subjected to ischemia or simulated ischemia, followed by reperfusion/reoxygenation. The end points were percent infarction/risk zone and annexin-V (apoptosis) and/or propidium iodide positivity (necrosis), respectively. In isolated hearts, 2-Cl-IB-MECA significantly limited infarct size (44.2 +/- 2.7% in control vs. 21.9 +/- 2.4% at 1 nM and 35.8 +/- 3.3% at 0.1 nM, P < 0.05). In isolated myocytes, apoptosis and necrosis were significantly reduced compared with controls (5.7 +/- 2.6% vs. 17.1 +/- 1.3% and 13.7 +/- 2.0% vs. 23.1 +/- 1.5%, respectively, P < 0.0001). In both models, the beneficial effects were abrogated using the A(3)R antagonist MRS-1191. The involvement of A(2a) receptor activation was also examined. This is the first study to demonstrate that A(3)R activation at reperfusion limits myocardial injury in the isolated rat heart and improves survival in isolated myocytes, possibly by antiapoptotic and antinecrotic mechanisms.
Helen L Maddock; Mihaela M Mocanu; Derek M Yellon
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  283     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-17     Completed Date:  2002-10-17     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1307-13     Citation Subset:  IM    
The Hatter Institute for Cardiovascular Studies, Division of Cardiology, University College London Hospitals and Medical School, United Kingdom.
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MeSH Terms
Adenosine / analogs & derivatives*,  pharmacology
Age Factors
Apoptosis / drug effects
Cardiotonic Agents / pharmacology
Cell Survival / drug effects
Dose-Response Relationship, Drug
Muscle Fibers, Skeletal / pathology
Myocardial Infarction / metabolism,  pathology
Myocardial Reperfusion Injury / metabolism*,  pathology
Myocardium / metabolism*,  pathology
Oxygen / pharmacology
Purinergic P1 Receptor Agonists
Rats, Sprague-Dawley
Receptor, Adenosine A3
Receptors, Purinergic P1 / metabolism*
Reg. No./Substance:
0/Cardiotonic Agents; 0/Purinergic P1 Receptor Agonists; 0/Receptor, Adenosine A3; 0/Receptors, Purinergic P1; 58-61-7/Adenosine; 7782-44-7/Oxygen; Z07JR07J6C/2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide

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