AMP579 is revealed to be a potent A2b-adenosine receptor agonist in human 293 cells and rabbit hearts.

摘要: The mixed A1/A2a-adenosine agonist AMP579 given at reperfusion is protective in animal models of myocardial infarction. Receptor-blocking studies have indicated that the protection came from an adenosine receptor (AR), but neither A1- nor A2a-selective agonists could duplicate its protection. We recently found A2b-selective are protective, and, therefore, tested whether might also be A2b agonist. used human embryonic kidney cells overexpressing receptors as assay system. In these cells, occupancy causes phosphorylation ERK. induced ERK with EC50 250 nM and this blocked by MRS1754 or PSB1115, two highly selective blockers receptors. attempted to confirm our hypothesis a rabbit heart model ischemia–reperfusion. (500 nM) for 1 h starting reduced infarct size isolated hearts exposed 30 min regional ischemia 2 (12.9 ± 2.2% infarction risk zone vs. 32.0 1.9% untreated hearts). PSB1115 first 15 AMP579’s (32.2 3.1% infarction) which consistent mechanism. conclude non-selective, potent A2b-AR agonist, against through receptor.