Molecular characterization of A1 and A2a adenosine receptors

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Abstract
Detailed amino acid sequence analyses of A1 and A2a adenosine receptors were assembled by analogy to other G‐protein‐coupled receptors and correlated with pharmacological observations. Sites for phosphorylation, palmitoylation, and sodium binding have been proposed. Striatal A2a receptors from human and other species were photoaffinity‐labeled using the selective, radioiodinated agonist PAPA‐APEC. Selective chemical affinity labels for A1 and A2a receptors have been introduced. For example, an isothiocyanate, ρ‐DITC‐APEC (100 nM), irreversibly diminished the Bmax for [3H]CGS 21680 (2‐[4‐[(2‐carboxyethyl) phenyl] ethylamino]‐5′‐N‐ethylcarboxamido‐adenosine) binding in rabbit striatal membranes by 71% (Kd unaffected), suggesting a direct modification of the ligand binding site. Novel trifunctional affinity labels have been designed. Rabbit and human A2a receptors were characterized using [3H]XAC binding in the presence of 50 or 25 nM CPX (8‐cyclopentyl‐1,3‐dipropylxanthine), respectively. The inhibition of A2 radioligand binding by the histidyl‐modifying reagent diethylpyrocarbonate suggested the involvement of His residues in interactions with adenosine agonists and antagonists. Properties of transiently expressed mutants of bovine A1 receptors in which either His251 or His278 residues have been substituted with Leu suggest that both histidines are important in binding.

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