Potentiation of the myocardial actions of adenosine in the presence of coformycin, a specific inhibitor of adenosine deaminase.
The effects of coformycin, a highly potent and specific inhibitor of the intracellular enzyme adenosine deaminase and the influence of dipyridamole, an inhibitor of the cellular adenosine uptake mechanism, were studied on the adenosine-induced changes in the electrical and mechanical activity of isolated electrically driven left atria of guinea-pig hearts. Adenosine (0.1 mumol/l-1 mmol/l) by itself elicited a concentration-dependent decrease in the action potential duration and contractile force of atrial preparations. Coformycin, when applied in a concentration inducing a nearly complete inhibition of adenosine deaminase activity in intact atrial myocardium (7 mumol/l), enhanced the adenosine-induced reduction both in the duration of the intracellularly recorded action potential and in the contractile force of the atria, preferentially at higher concentrations of adenosine (10 mumol/l-1 mmol/l). The calculated half recovery time during wash-out (t1/2) was found to be about 6 times longer than that of controls (317.5 +/- 47 and 51.3 +/- 4.3 sec, respectively). In contrast with adenosine, the action of 2-chloroadenosine (an adenosine deaminase resistant purine derivative) on the atrial contractile force was not affected in the presence of coformycin. Dipyridamole (0.3 mumol/l) was capable of significantly potentiating the adenosine-induced depression of atrial mechanical activity, mainly at lower concentrations of adenosine (0.1-10 mumol/l). Preincubation of atrial preparations with a combination of coformycin and dipyridamole produced a strong enhancement in the adenosine-induced decrease of mechanical activity at all concentrations of adenosine. It is suggested that adenosine might exert its myocardial actions not only through the known extracellular, but also via possible intracellular purinoceptors.
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D003070:Coformycin / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D012263:Ribonucleosides / Q000494:pharmacology*
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D004176:Dipyridamole; D009700:Nucleoside Deaminases; D000241:Adenosine