Evidence that adenosine receptors in the dog left atrium are not of the typical A1 or A2 adenosine receptor subtypes.

The adenosine receptors from the isolated dog left atrium were characterized using the non-selective agonists 5'-N-ethyl-carboxamidoadenosine (NECA) and adenosine, the A1-selective agonist N6-R-phenylisopropyladenosine (R-PIA), and the A2 adenosine receptor agonist C2-naphthylethoxyadenosine (NEA). The potency order of the agonists in the dog left atrium was NECA greater than adenosine greater than R-PIA = NEA. This potency order was the same as that found in the guinea pig aorta (A2) but different from that in the guinea pig left atrium (A1). In the guinea pig left atrium the potency order was NECA greater than R-PIA greater than adenosine much greater than NEA. The negative inotropic responses to NECA in the dog left atrium were antagonised by the non-selective antagonist 8-phenyltheophylline (8-PT) and the A1-selective antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and N6-endonorbornan-2-yl-9-methyladenine (N-0861), giving pKB values of 6.3, 7.3 and 5.1, respectively. These values are significantly different from those estimates determined in either the guinea pig left atrium or guinea pig aorta. The potency order of the agonists and the relatively low potencies of the A1-selective antagonists suggests that the adenosine receptors in the dog left atrium are not of the classical A1 adenosine receptor subclass and may instead be more closely related to the A2 adenosine receptor.