The structure and function of A 1 and A 2B adenosine receptors

Abstract

Of the four G protein coupled adenosine receptor (AR) subtypes, the A 1 is best suited for studies of reconstitution with G proteins. Recombinant A 1 receptors extended with hexahistidine and FLAG have been purified to near homogeneity. In reconstitution assays using pure recombinant G protein subunits, the composition of the γ subunit influences coupling to purified A 1ARs. The least well characterized AR is the A 2B. New data indicate that A 2BARs can trigger the degranulation of canine and human mast cell lines. Recombinant human A 2BARs are blocked by the anti-asthma drugs theophylline and enprofylline at concentrations that are used therapeutically to treat asthma. Although A 2BARs have long been known to stimulate adenylyl cyclase, they also can activate phospholipase C and mobilize Ca 2+ by signaling through Gq/11. There is great potential for new therapies based on compounds that selectively target individual AR subtypes.