THE STRUCTURE AND FUNCTION OF A(1) AND A(2B) ADENOSINE RECEPTORS

Of the four G protein coupled adenosine receptor (AR) subtypes, the A( 1) is best suited for studies of reconstitution with G proteins. Recom binant A(1) receptors extended with hexahistidine and FLAG have been p urified to near homogeneity. In reconstitution assays using pure recom binant G protein subunits, the composition of the gamma subunit influe nces coupling to purified A(1)ARs. The least well characterized AR is the A(2B). New data indicate that A(2B)ARs can trigger the degranulati on of canine and human mast cell lines. Recombinant human A(2B)ARs are blocked by the anti-asthma drugs theophylline and enprofylline at con centrations that are used therapeutically to treat asthma. Although A( 2B)ARs have long been known to stimulate adenylyl cyclase, they also c an activate phospholipase C and mobilize Ca2+ by signaling through Gq/ 11. There is great potential for new therapies based on compounds that selectively target individual AR subtypes.