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

Peart, Jason, Willems, Laura, and Headrick, John P. (2003) Receptor and non-receptor-dependent mechanisms of cardioprotection with adenosine. American Journal of Physiology-Heart and Circulatory Physiology, 284 (2). pp. 519-527.

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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.

Item ID: 10106
Item Type: Article (Refereed Research - C1)
Keywords: ischemia-reperfusion; mitochondrial adenosine 5-triphosphate- sensitive K channel; mouse; protein kinase C
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ISSN: 1522-1539
Date Deposited: 17 Apr 2010 04:42
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 50%
06 BIOLOGICAL SCIENCES > 0606 Physiology > 060699 Physiology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970102 Expanding Knowledge in the Physical Sciences @ 50%
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