PHARMACOLOGICAL CLASSIFICATION OF ADENOSINE RECEPTORS IN THE SINOATRIAL AND ATRIOVENTRICULAR NODES OF THE GUINEA-PIG

1 The effects of seven agonist and three antagonist adenosine receptor ligands were compared on the guinea-pig sinoatrial (SA) node (isolate d right atrium) and atrioventricular (AV) node (perfused whole heart). Single agonist concentration-effect curves were obtained to 5'-N-ethy lcarboxamidoadenosine (NECA), R(-)-N-6-(2-phenylisopropyl)adenosine (R PIA), N-6-cyclohexyladenosine (CHA), 2-chloroadenosine (CADO),),S(+)-N -6-(2-phenylisopropyl) adenosine (L-PIA), 2-phenylaminoadenosine (CV 1 808) and N-6-aminoadenosine (MeAdo). Adenosine and/or NECA curves were obtained in the absence and presence of the antagonists 8-cyclopentyl -1,3-dipropylxanthine (DPCPX), 9-chloro-2-(2-furany1)-5,6-dihydro- 1,2 ,4- triazolo [1,5 c]quinazolin-5-imine (CGS 15943) and N-6-(endonorbor nan-2-yl)-9-methyladenine (N-0861). 2 A formal comparison of the agoni st and antagonist potency data was made by fitting the data to a strai ght line using a least squares procedure based on principal components analysis to account for the variance on both axes. The antagonist aff inity estimates made on the two assays did not deviate significantly f rom the line of identity. 3 The agonist p[A](50) data obtained on the two assays did not deviate from the line of identity, indicating that there were no significant differences in potencies between the two ass ays. The P[A](50) ratio of R-PIA and S-PIA was 1.24+/-0.09 in the SA n ode and 1.36+/-0.11 in the AV node, indicating no difference in the st ereoselectivity of the PIA isomers between the two tissues. 4 The agon ist potency and antagonist affinity data obtained are consistent with previous findings showing that the AV and SA node data are pharmacolog ically indistinguishable and belong to the adenosine A(1)-receptor cla ss. No evidence for the reported A(3)-receptor was found.