Receptor and non-receptor-dependent mechanisms of cardioprotection with adenosine

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Title Receptor and non-receptor-dependent mechanisms of cardioprotection with adenosine
Author Peart, Jason Nigel John; Willems, Laura; Headrick, John Patrick
Journal Name American Journal of Physiology: Heart and Circulatory Physiology
Year Published 2003
Place of publication USA
Publisher American Physiological Society
Abstract The relative roles of mitochondrial (mito) ATP-sensitive K+ (mitoKATP) channels, protein kinase C (PKC), and adenosine kinase (AK) in adenosine-mediated protection were assessed in Langendorff-perfused mouse hearts subjected to 20-min ischemia and 45-min reperfusion. Control hearts recovered 72 ± 3 mmHg of ventricular pressure (50% preischemia) and released 23 ± 2 IU/g lactate dehydrogenase (LDH). Adenosine (50 μM) during ischemia-reperfusion improved recovery (149 ± 8 mmHg) and reduced LDH efflux (5 ± 1 IU/g). Treatment during ischemia alone was less effective. Treatment with 50 μM diazoxide (mitoKATP opener) during ischemia and reperfusion enhanced recovery and was equally effective during ischemia alone. A3 agonism [100 nM 2-chloro-N 6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide], A1 agonism (N 6-cyclohexyladenosine), and AK inhibition (10 μM iodotubercidin) all reduced necrosis to the same extent as adenosine, but less effectively reduced contractile dysfunction. These responses were abolished by 100 μM 5-hydroxydecanoate (5-HD, mitoKATP channel blocker) or 3 μM chelerythrine (PKC inhibitor). However, the protective effects of adenosine during ischemia-reperfusion were resistant to 5-HD and chelerythrine and only abolished when inhibitors were coinfused with iodotubercidin. Data indicate adenosine-mediated protection via A1/A3 adenosine receptors is mitoKATP channel and PKC dependent, with evidence for a downstream location of PKC. Adenosine provides additional and substantial protection via phosphorylation to 5′-AMP, primarily during reperfusion.
Peer Reviewed Yes
Published Yes
Publisher URI
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
Volume 284
Page from 519
Page to 527
ISSN 0363-6135
Date Accessioned 2004-04-07
Date Available 2015-02-05T03:42:25Z
Language en_US
Research Centre Menzies Health Institute Qld; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Cardiology (incl. Cardiovascular Diseases)
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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