Receptor Coupling to effector system Body distribution Physiological function   A1   G Protein-coupled: Gi Adenylatecyclase: ↓cAMP Kinase pathways: PKC, MAPK,  PI3K Ion channels: ↑K+, ↓Ca2+   Broad distribution: high in nerves, heart, kidney and adipose tissue   Decreased renal blood flow, inhibition of renin release, inhibition of lipolysis, increased systemic blood pressure, vasoconstriction, bronchoconstriction, inhibition of neurotransmitter release, inhibition of insulin and glucagon release, reduced heart rate, sleep, analgesia, cardiac preconditioning   A2A   G Protein-coupled: Gs Adenylatecyclase: ↑cAMP   Broad distribution: very high in basal ganglia; high in nerves, blood vessels, kidney and immune cells   Wakefulness and locomotion, increased renal flow, immunosuppression, vasodilation and hypotension, coronary vasodilation, angiogenesis, cardioprotection, baroreflex control  A2B G Protein-coupled: Gs, Gq/11 Adenylatecyclase: ↑cAMP Phospholipase C: ↑↓IP3, ↑Ca2+ Broad distribution, but generally low abundance Vascular integrity, cardiac preconditioning, pro-inflammation (acute injury) and anti-inflammation (some chronic disease states), fibrosis A3 G Protein-coupled: Gi Adenylatecyclase: ↓cAMP kinase pathways: MAPK,  PI3K Phospholipase D, RhoA and Wnt pathways Restricted distribution, varying in different species: high in mast cells Increased mast cell activation, airway contraction, inflammatory pain, white cell chemotaxis, chronic neuropathic pain relief, anticancer (melanoma)

Table 1: Classification, distribution and physiological function of the adenosine receptors [34,35,57,96,97,114,120]. cAMP, cyclic adenosine monophosphate; PKC, protein kinase C, MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3 kinase; IP3, inositol triphosphate; RhoA, Ras homolog gene family member A.