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

Abstract

(−)‐N6‐phenylisopropyladenosine (R‐PIA) and N6‐cyclohexyladenosine (CHA), highly selective agonists at A1‐adenosine receptors, 5′‐N‐ethyl‐carboxamidoadenosine (NECA), a non‐selective agonist at A1 and A2 receptors, and 2‐phenylaminoadenosine (CV‐1808), a selective A2 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. 1,3‐Dipropyl‐8‐cyclopentylxanthine (DPCPX), a new selective A1 receptor antagonist, competitively inhibited the effects of the adenosine agonists, at low concentrations (IC50 < 1 nm). CHA and NECA were able to inhibit the positive inotropic effect of Bay K 8644 both in spontaneously beating and in electrically driven atria. R‐PIA, CHA and NECA (agonists), 8‐phenyltheophylline (PT) and DPCPX (antagonists), failed to influence [3H]‐nitrendipine binding on microsomal membranes from guinea‐pig atria and ventricles in a range of concentrations from 1 nM to 100 μm. The data support the existence of A1 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 A1 receptors. 1989 British Pharmacological Society