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Pharmacological classification of adenosine receptors in the sinoatrial and atrioventricular nodes of the guinea‐pig
Author(s) -
Meester B J,
Shankley N P,
Welsh N J,
Wood J,
Meijler F L,
Black J W
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701891
Subject(s) - sinoatrial node , agonist , adenosine , adenosine receptor , antagonist , chemistry , adenosine a1 receptor , atrioventricular node , medicine , endocrinology , partial agonist , stereochemistry , receptor , pharmacology , biochemistry , heart rate , blood pressure , tachycardia
The effects of seven agonist and three antagonist adenosine receptor ligands were compared on the guinea‐pig sinoatrial (SA) node (isolated right atrium) and atrioventricular (AV) node (perfused whole heart). Single agonist concentration‐effect curves were obtained to 5′‐N‐ethylcarboxamidoadenosine (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 1808) 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‐furanyl)‐5,6‐dihydro‐1,2,4‐triazolo[1,5‐c]quinazolin‐5‐imine (CGS15943) and N 6 ‐(endonorbornan‐2‐yl)‐9‐methyladenine (N‐0861). A formal comparison of the agonist and antagonist potency data was made by fitting the data to a straight line using a least squares procedure based on principal components analysis to account for the variance on both axes. The antagonist affinity estimates made on the two assays did not deviate significantly from the line of identity. 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 assays. The p[A] 50 ratio of R ‐PIA and S ‐PIA was 1.24±0.09 in the SA node and 1.36±0.11 in the AV node, indicating no difference in the stereoselectivity of the PIA isomers between the two tissues. The agonist potency and antagonist affinity data obtained are consistent with previous findings showing that the AV and SA node data are pharmacologically indistinguishable and belong to the adenosine A 1 ‐receptor class. No evidence for the reported A 3 ‐receptor was found.