Effects of adenosine and adenine nucleotides on the atrioventricular node of isolated guinea pig hearts.
The primary goal of this study was to determine whether the slowing of atrioventricular (AV) conduction by ATP is caused by ATP per se or is mediated by adenosine formed from ATP degradation. We assessed the effects of ATP, beta, gamma-methylene ATP, ADP, AMP, and adenosine on AV conduction time in the isolated perfused guinea pig heart. The cardiac effluent was collected and analyzed for its content of adenine nucleotides and nucleosides. Perfused ATP was rapidly and almost completely broken down to AMP and adenosine; only 2.5 +/- 0.5% of the infused ATP was recoverable in the effluent. A significant correlation was found between the effluent concentration of adenosine and atria-to-His bundle (A-H) conduction time. Compounds that altered the effect of adenosine on A-H conduction likewise altered the effect of ATP: (1) aminophylline, a competitive antagonist of adenosine, antagonized the ATP-induced A-H prolongation; (2) adenosine deaminase, the enzyme responsible for the deamination of adenosine to inosine, reduced the effect of ATP by 82%; (3) the adenosine transport blockers NBMPR and dipyridamole markedly enhanced the effect of ATP; and (4) EHNA, an inhibitor of adenosine deaminase, potentiated the effect of ATP. Furthermore, the less hydrolyzable ATP analog, beta, gamma-methylene ATP, was less potent than ATP in causing A-H prolongation. We conclude that the adenosine-like action of ATP on the guinea pig AV node requires that ATP first be degraded to adenosine.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006168:Guinea Pigs; D006327:Heart Block / Q000139:chemically induced; D006329:Heart Conduction System / Q000502:physiology*; D066298:In Vitro Techniques; D009705:Nucleosides / Q000037:antagonists & inhibitors; D013997:Time Factors
D000227:Adenine Nucleotides; D058892:Adenosine Deaminase Inhibitors; D009705:Nucleosides; D000628:Aminophylline; C010192:9-(2-hydroxy-3-nonyl)adenine; D004176:Dipyridamole; D001285:Atropine; D000243:Adenosine Deaminase; D000225:Adenine; D000241:Adenosine