and to increase coronary circulation by vasodilation. In addition, A2A receptor can suppress immune cells, thereby protecting tissue from inflammation. The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, and Parkinson's disease. Ligands A number of selective A2A ligands have been developed, with several possible therapeutic applications. Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused mainly on the role of adenosine receptors in the heart, and led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest. However the development of more highly selective A2A ligands has led towards other applications, with the most significant focus of research currently being the potential therapeutic role for A2A antagonists in the treatment of Parkinson's disease. Agonists ATL-146e YT-146/2-octynyladenosine CGS-21680 DPMA (N6-(2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)adenosine) Regadenoson UK-432,097 Limonene Zeatin riboside NECA (5′-(N-Ethylcarboxamido)adenosine) binodenoson Cannabidiol Antagonists ATL-444 Istradefylline (KW-6002) MSX-3 Preladenant (SCH-420,814) SCH-58261 SCH-412,348 SCH-442,416 ST-1535 Caffeine VER-6623 VER-6947 VER-7835 Vipadenant (BIIB-014) ZM-241,385 Interactions Adenosine A2A receptor has been shown to interact with Dopamine receptor D2. As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. In cancer immunotherapy The adenosine A2A receptor has also been shown to play a regulatory role in the adaptive immune system. In this role, it functions similarly to programmed cell death-1 (PD-1) and cytotoxic t-lymphocyte associated protein-4 (CTLA-4) receptors, namely to suppress immunologic response and prevent associated tissue damage. Extracellular adenosine gathers in response to cellular stress and breakdown through interactions with hypoxia induced HIF-1α. Abundant extracellular adenosine can then bind to the A2A receptor resulting in a Gs-protein coupled response, resulting in the accumulation of intracellular cAMP, which functions primarily through protein kinase A to upregulate inhibitory cytokines such as transforming growth factor-beta (TGF-β) and inhibitory receptors (i.e., PD-1). Interactions with FOXP3 stimulates CD4+ T-cells into regulatory Treg cells further inhibiting immune response. Blockade of A2AR has been attempted to various ends, namely cancer immunotherapy. While several A2A receptor antagonists have progressed to clinical trials for the treatment of Parkinson's disease, A2AR blockade in the context of cancer is less characterized. Mice treated with A2AR antagonists, such as ZM241385 (listed above) or caffeine, show significantly delayed tumor growth due to T-cells resistant to inhibition. This is further highlighted