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dc.contributor.authorWee, Shirleyen_US
dc.contributor.authorHeadrick, Johnen_US
dc.contributor.authorPeart, Jasonen_US
dc.contributor.editorDr. R. A. Walsh (Editor-in-Chief)en_US
dc.description.abstractP2 purinoceptor-dependent control of resistance to ischemia reperfusion injuries was studied in Langendorff perfused C57/Bl6 mouse hearts subjected to 20 min ischemia and 45 min reperfusion. Effects of P2 agonism and antagonism were assessed. Control hearts recovered 68 ᠴ mm Hg ventricular pressure (63 ᠳ% pre-ischaemia), exhibited sustained diastolic contracture (23 ᠲ mm Hg), and released 26 ᠴ U/g lactate dehydrogenase (LDH) during reperfusion, evidencing oncosis. Treatment with 250 nM of the P2 agonist uridine 5'-triphosphate (UTP) for 10 min prior to and 10 min after ischemia reduced diastolic contracture by not, vert, similar 50% (9 ᠲ mm Hg), improved pressure development (85 ᠵ mm Hg; 77 ᠲ% of baseline), and reduced LDH loss by 60% (11 ᠲ U/g). In contrast, P2Y1 agonism with 50 nM 2-methyl-thio-ATP was ineffective. P2 antagonism with 200 占suramin impaired post-ischemic outcomes, exaggerating contractile dysfunction (41 ᠲ mm Hg diastolic pressure; 33 ᠵ mm Hg developed pressure) and LDH loss (53 ᠹ U/g). In the presence of suramin, UTP no longer modified post-ischemic function or oncosis. Evidence of intrinsic P2-mediated protection is consistent with ischemic elevations in microdialysate [UTP], [ATP] and [ADP]. In summary, these data evidence myocardial protection via endogenous and exogenous P2 agonists: enhanced recoveries with UTP, together with exaggeration of intrinsic injury and inhibition of UTP-protection with suramin, support protection via exogenously and intrinsically activated P2 purinoceptors. Data implicate P2Y2 receptors in cardioprotection, though further work is required to identify the sub-type involved.en_US
dc.publisherAcademic Pressen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofissue6 Supp1en_US
dc.relation.ispartofjournalJournal of Molecular and Cellular Cardiologyen_US
dc.subject.fieldofresearchCardiology (incl. Cardiovascular Diseases)en_US
dc.titleIntrinsic and extrinsic P2 purinoceptor-mediated cardioprotection in miceen_US
dc.typeJournal articleen_US
dc.type.descriptionC3 - Letter or Noteen_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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