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dc.contributor.authorPeart, Jasonen_US
dc.contributor.authorWillems, Lauraen_US
dc.contributor.authorHeadrick, Johnen_US
dc.description.abstractThe 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 ᠳ mmHg of ventricular pressure (50% preischemia) and released 23 ᠲ IU/g lactate dehydrogenase (LDH). Adenosine (50 卩 during ischemia-reperfusion improved recovery (149 ᠸ mmHg) and reduced LDH efflux (5 ᠱ IU/g). Treatment during ischemia alone was less effective. Treatment with 50 占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 占iodotubercidin) all reduced necrosis to the same extent as adenosine, but less effectively reduced contractile dysfunction. These responses were abolished by 100 占5-hydroxydecanoate (5-HD, mitoKATP channel blocker) or 3 占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.en_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.ispartofjournalAmerican Journal of Physiology: Heart and Circulatory Physiologyen_US
dc.titleReceptor and non-receptor-dependent mechanisms of cardioprotection with adenosineen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightSelf-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.en_US
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