Effect of selective agonists and antagonists on atrial adenosine receptors and their interaction with Bay K 8644 and [ 3 H]‐nitrendipine

1 (−)‐N 6 ‐phenylisopropyladenosine (R‐PIA) and N 6 ‐cyclohexyladenosine (CHA), highly selective agonists at A 1 ‐adenosine receptors, 5′‐N‐ethyl‐carboxamidoadenosine (NECA), a non‐selective agonist at A 1 and A 2 receptors, and 2‐phenylaminoadenosine (CV‐1808), a selective A 2 agonist, were compared in spontaneously beating and electrically driven atria. R‐PIA, CHA and NECA inhibited contraction in both preparations. CV‐1808 was not effective up to 500 nM. 2 1,3‐Dipropyl‐8‐cyclopentylxanthine (DPCPX), a new selective A 1 receptor antagonist, competitively inhibited the effects of the adenosine agonists, at low concentrations (IC 50 < 1 n m ). 3 CHA and NECA were able to inhibit the positive inotropic effect of Bay K 8644 both in spontaneously beating and in electrically driven atria. 4 R‐PIA, CHA and NECA (agonists), 8‐phenyltheophylline (PT) and DPCPX (antagonists), failed to influence [ 3 H]‐nitrendipine binding on microsomal membranes from guinea‐pig atria and ventricles in a range of concentrations from 1 nM to 100 μ m . 5 The data support the existence of A 1 receptors in atrial tissue. No evidence for a direct interaction between adenosine analogues and Bay K 8644 was found at the level of slow calcium channels. Adenosine analogues appear to antagonize the effects of Bay K 8644 indirectly by activation of A 1 receptors.