Cloning of a chick A3 adenosine receptor:: characterization of ligand binding and receptor-effector coupling of chick A1 and A3 adenosine receptors

We have reported previously the cloning and partial characterization of a chick A(1) adenosine receptor expressed in the heart. We report herein the cloning of a chick A(3) adenosine receptor and a comprehensive characterization of both the A(1) and A(3) receptors expressed in human embryonic kidney 293 cells. [I-125]N-6-(p-aminobenzyl)adenosine bound to both receptors with similar affinities and was used in competition studies. Although the selectivities of both agonists and antagonists were less than in other species, two antagonists, 3-ethyl-5-benzyl-2methyl-6-phenyl-4-phenylethynal-(+/-)-dihy3,5-dicarboxylate and 3,6-dichloro-2'-(isopropyroxy)-4'-methylflavone), were at least partially selective for A(3) receptors while one antagonist [C-8-(N-methylisopropyl)-amine-N-6-(5'-endohydroxy)endonorboman-2-yl-9-methyladenine] was selective for A, receptors. While both receptors coupled to the inhibition of adenylyl cyclase, we were unable to detect coupling of either receptor to phospholipase C or D.