Adenosine is an endogenous nucleoside generated locally in tissues under conditions of hypoxia, ischemia, or inflammation. It modulates a variety of physiological functions in many tissues including the brain and heart.^1,2 Adenosine exerts its actions via four specific adenosine receptors (also named P1 purinergic receptors): Adenosine A₁ Receptor (A₁AR), Adenosine A_2A Receptor (A_2AAR), Adenosine A_2B Receptor (A_2BAR), and Adenosine A₃ Receptor (A₃AR). All are integral membrane proteins and are members of the G protein-coupled receptor superfamily. They share a common structure of seven putative transmembrane domains, an extracellular amino terminus, a cytoplasmic carboxyl terminus, and a third intracellular loop that is important for binding G proteins.^1-3 The adenosine receptors can be distinguished on the basis of their differential selectivity for adenosine analogs.^1-3

A₁AR is widely distributed and has been well characterized. High expression of A₁AR is found in the brain (mainly in the cortex, cerebellum, and hippocampus), dorsal horn of the spinal cord, adrenal gland, and atria, and to a lower extent in several other tissues including adipose tissue, the colon, and kidney.^2,4

A₁AR modulates the activity of several ion channels. Activation of A₁AR (by adenosine, its major agonist) inhibits N-type Ca²⁺ channels via a voltage-dependent, pertussis toxin (PTX)-sensitive pathway in neurons of the rat major pelvic ganglia (MPG).⁵

Since A₁AR is the most prominent adenosine receptor in adipocytes, it has become a natural target for research on obesity, which is a major health problem.^6,7 A possible role in cell proliferation and carcinogenesis has also been suggested for A₁AR.^8,9