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Evidence for a cooperation between adenosine A 2 receptors and β 1 ‐adrenoceptors on cardiac automaticity in the isolated right ventricle of the rat
Author(s) -
Hernandez J.,
Figueira M.A.,
Ribeiro J.A.,
Pinto F.
Publication year - 1994
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 - 10.1111/j.1476-5381.1994.tb14888.x
Subject(s) - adenosine , medicine , cgs 21680 , adenosine a1 receptor , endocrinology , adenosine receptor , isoprenaline , agonist , adenosine receptor antagonist , receptor , chemistry , biology , stimulation
1 The effects of the adenosine receptor agonists, 5′‐N‐ethyl‐carboxamidoadenosine (NECA) and 2‐[4‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS‐21680) on ventricular automaticity induced by a local injury in the isolated right ventricle of the rat were studied. 2 In concentrations ranging from 0.1 to 100 n m , NECA significantly increased ventricular automaticity. This effect was more reproducible when the adenosine receptor antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX) was present at 5 n m , a concentration that blocks A 1 adenosine receptors. 3 The excitatory effect of NECA was not observed when DPCPX was present at a concentration of 10 μ m , which antagonizes both A 1 and A 2 adenosine receptors, as well as when rats were reserpinized. 4 In reserpinized rats, NECA increased ventricular automaticity in the presence of isoprenaline and the β 2 ‐adrenoceptor antagonist, ICI‐118,551, but not in the presence of the β r adrenoceptor antagonists, bisoprolol or atenolol. 5 The A 2a ‐selective adenosine receptor agonist, CGS‐21680 (0.1 n m ‐10 μ m ) was devoid of excitatory effect on ventricular automaticity. Binding studies of this compound to the rat ventricular membranes revealed that in the preparation there was no specific binding. 6 These results suggest that the excitatory effect of NECA on ectopic ventricular automaticity is dependent on endogenous catecholamines and is mediated by an A 2 adenosine receptor which is in some way ‘linked’ to the β 1 ‐adrenoceptor. These A 2 receptors do not appear to be of the A 2a adenosine receptor subtype.