Adenosine mediates the negative chronotropic action of adenosine 5'-triphosphate in the canine sinus node.
ATP exerts pronounced electrophysiologic effects in the mammalian heart. The present study tested the hypothesis that the negative chronotropic action of ATP in the canine sinus node is dependent on its degradation to adenosine. Increasing doses of the following compounds were administered in the sinus nodal artery of 12 open chest dogs (either sex, 30-35 kg) anesthetized with pentobarbital (30 mg/kg i.v.): adenosine, ATP, alpha,beta methylene-ATP (AMPCPP) and beta,gamma methylene-ATP (AMPPCP). Right atrial, His bundle and right ventricular electrograms as well as Lead II ECG and systemic arterial blood pressure were monitored continuously and recorded. The depressant effects of test compounds on the sinus node were assessed from the prolongation of sinus cycle length and the duration of junctional escape rhythm which they induced. Data were used to plot dose-response curves for the four test compounds. The order of potency was adenosine greater than or equal to ATP greater than or equal to AMPPCP much greater than AMPCPP = 0. In 3 of 12 dogs the emergence of junctional escape rhythm was observed after the highest dose of either adenosine, ATP or AMPPCP. In addition, aminophylline, a selective competitive inhibitor of adenosine at P1-purinoceptor site, reduced the effects of maximal doses of adenosine, ATP and AMPPCP by 52 +/- 7, 67 +/- 8 and 72 +/- 6%, respectively (each, P less than .05; AMPPCP vs. adenosine, P less than .05). The present data indicate that the negative chronotropic action of ATP is due to its rapid catabolism to adenosine and the action of adenosine at P1-purinoceptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Pelleg
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Lankenau Medical Research Center, Philadelphia, Pennsylvania.
Mitsuoka
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T
Michelson
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Menduke
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D000241:Adenosine / Q000032:analysis / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011983:Receptors, Purinergic / Q000187:drug effects
D011983:Receptors, Purinergic; D000628:Aminophylline; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate