Protein Kinase C Protects Preconditioned Rabbit Hearts by Increasing Sensitivity of Adenosine A2b-Dependent Signaling During Early Reperfusion

摘要: Although protein kinase C (PKC) plays a key role in ischemic preconditioning (IPC), the actual mechanism of that protection is unknown. We recently found from IPC requires activation adenosine receptors during early reperfusion. We, therefore, hypothesized PKC might act to increase heart's sensitivity adenosine. limited infarct size isolated rabbit hearts subjected 30-min regional ischemia/2-h reperfusion and IPC's was blocked by inhibitor chelerythrine given revealing involvement at Similarly infused period increased phosphorylation protective kinases Akt ERK1/2 observed after IPC. Infusing phorbol 12-myristate 13-acetate (PMA), activator, mimicked protection. As expected, triggered PMA chelerythrine, but surprisingly it also MRS1754, an A2b receptor-selective antagonist, suggesting somehow facilitating signaling receptors. NECA [5′-(N-ethylcarboxamido) adenosine], potent not selective receptor agonist, dose-dependent manner. Pretreating with or brief ischemia had no effect on per se markedly lowered threshold for induce their phosphorylation. BAY 60-6583, highly caused Akt. MRS1754 prevented induced 60-6583. 60-6583 when These results suggest cardiac protective, because very low affinity endogenous unable trigger signaling. propose event occurs increases so can activate A2b-dependent