Characterization of cardiac adenosine receptors using N6-phenyladenosines and a new radioligand, [125I]-(m-aminophenyl)adenosine

The chick heart contains adenosine receptors with characteristics similar to the R adenosine receptors found in the CNS. They have synthesized several N6-phenyladenosines and tested their potencies for inhibiting the binding of [125I](p-aminobenzyl)adenosine {[125I]ABA) to chick heart membranes. Of the 12 compounds tested, N6-(p-aminobenzyl) adenosine (ABA) was the least potent (IC50 ∼ 40 nM) while N6-(m-nitrophenyl)adenosine(MNPA) was the most potent (IC50 ∼ 1 nM). The IC50 of N6-(m-aminophenyl)adenosine(MAPA) was greater than that of N6-phenyladenosine(PA) while that of MNPA was less than that of PA. The effects of these electron-releasing (-NH2) and electron-withdrawing (-NO2) groups along with data obtained with other phenyl-substituted N6-phenyladenosines suggest that the electron density of the N6-nitrogen may affect the affinities of these compounds for the cardiac adenosine receptor. MAPA can be iodinated to produce a new ligand, [125I]MAPA. This iodination, like that of ABA, increases the affinity of the compound and produces a ligand with good affinity and low nonspecific binding suitable for studies on tissues with low concentrations of adenosine receptors