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

Abstract.

We have reported previously the cloning and partial characterization of a chick A₁ adenosine receptor expressed in the heart. We report herein the cloning of a chick A₃ adenosine receptor and a comprehensive characterization of both the A₁ and A₃ receptors expressed in human embryonic kidney 293 cells. [¹²⁵I]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-2-methyl-6-phenyl-4-phenylethynal-(±)-dihydropyridine-3,5-dicarboxylate and 3,6-dichloro-2′-(isopropyloxy)-4′-methylflavone), were at least partially selective for A₃ receptors while one antagonist [C⁸-(N-methylisopropyl)-amine-N ⁶-(5′endohydroxy)endonorbornan-2-yl-9-methyladenine] was selective for A₁ 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.