Purinergic P2Y receptors (P2R) belong to a large family of receptors activated with extracellular purine and pyrimidine nucleotides. As G protein-coupled receptors they induce Ca²⁺ release from intracellular stores that is followed by activation of several signaling pathways and various cellular responses, such as proliferation, apoptosis or cytokine release. The biological significance of endothelial P2YR has been revealed only recently by showing their role in vascular inflammation, wound healing, angiogenesis and atherosclerosis. We were the first to demonstrate that activation of endothelial P2YR increased intracellular free calcium ion concentrations, induced phosphorylation of focal adhesion kinase (FAK), p130(cas) and paxillin, caused upregulation of α(v) integrin expression and triggered cytoskeletal rearrangements followed by cell migration. Furthermore, we have evidence indicating that endothelial P2YR are linked to AMP-activated protein kinase (AMPK) signaling pathway. AMPK is the key molecule regulating cellular metabolism and is of critical importance in clinical management of type 2 diabetes. Another newly described by us role of P2YR is activation of endothelial nitric oxide synthase (eNOS) that catalyzes the production of nitric oxide (NO) and as such is particularly important for vascular function. It is well established that human endothelium plays a crucial role in the vascular homeostasis and both immune and inflammatory responses, and that likely endothelial P2YR are involved in these processes. Therefore, we propose that P2YR should be recognized as good targets for a pharmacological intervention. Especially that regardless of ubiquitous distribution of various P2 receptors in cells, pharmacological antagonists/agonists of P2R have already been successfully applied clinically, including antiplatelet drug, clopidogrel.

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