Evidence for a cooperation between adenosine A2 receptors and beta 1-adrenoceptors on cardiac automaticity in the isolated right ventricle of the rat.
1. The effects of the adenosine receptor agonists, 5'-N-ethyl-carboxamidoadenosine (NECA) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosin e (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 nM, 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 nM, a concentration that blocks A1 adenosine receptors. 3. The excitatory effect of NECA was not observed when DPCPX was present at a concentration of 10 microM, which antagonizes both A1 and A2 adenosine receptors, as well as when rats were reserpinized. 4. In reserpinized rats, NECA increased ventricular automaticity in the presence of isoprenaline and the beta 2-adrenoceptor antagonist, ICI-118,551, but not in the presence of the beta 1-adrenoceptor antagonists, bisoprolol or atenolol. 5. The A 2s-selective adenosine receptor agonist, CGS-21680 (0.1 nM-10 microM) 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 A2 adenosine receptor which is in some way 'linked' to the beta 1-adrenoceptor. These A2 receptors do not appear to be of the A2a adenosine receptor subtype.
Department of Pharmacology, Medical School, Murcia, Spain.
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J
Hernandez
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F
Pinto
M A
MA
Figueira
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JA
Riberio
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D016276:Ventricular Function; D014970:Xanthines / Q000494:pharmacology
D010627:Phenethylamines; D018342:Receptors, Adrenergic, beta-1; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D007545:Isoproterenol