Evidence that adenosine receptors in the dog left atrium are not of the typical A 1 or A 2 adenosine receptor subtypes

Abstract

The adenosine receptors from the isolated dog left atrium were characterized using the non-selective agonists 5′-N-ethyl-carboxamidoadenosine (NECA) and adenosine, the A 1-selective agonist N 6-R-phenylisopropyladenosine (R-PIA), and the A 2 adenosine receptor agonist C 2-naphthylethoxyadenosine (NEA). The potency order of the agonists in the dog left atrium was NECA > adenosine > R-PIA = NEA. This potency order was the same as that found in the guinea pig aorta (A 2) but different from that in the guinea pig left atrium (A 1). In the guinea pig left atrium the potency order was NECA > R-PIA > adenosine ⪢ 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 A 1-selective antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and N 6-endonorbornan -2-yl-9-methyladenine (N-0861), giving pK B 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 A 1-selective antagonists suggests that the adenosine receptors in the dog left atrium are not of the classical A 1 adenosine receptor subclass and may instead be more closely related to the A 2 adenosine receptor.