Potentiation by dilazep on the negative inotropic effect of adenosine on guinea-pig atria.
1 Dilazep, a coronary dilator, has been reported to potentiate the negative inotropic and negative chronotropic responses of guinea-pig atria to adenosine. Studies were made on the mechanism of the potentiating action of dilazep with special reference to the degradation and uptake of adenosine. 2 The negative inotropic actions of adenosine and adenine nucleotides, such as ATP, ADP, AMP and cyclic AMP, on guinea-pig atria were selectively and dose-dependently augmented by dilazep at concentrations insufficient to produce any effect alone (0.01 to 1 microM). 3 Incubation of atrial tissue with 8.8 nM adenosine, containing 0.1 microCi of [3H]-adenosine, resulted in accumulation of [3H]-adenosine in the tissue; dilazep (0.01 to 1 microM) inhibited this accumulation. 4 Adenosine (10 microM to 10 mM) was degraded to inosine and hypoxanthine during incubation with atrial tissue; dilazep (0.1 to 10 microM) retarded the disappearance of adenosine and the formation of inosine and hypoxanthine. 5 These results suggest that dilazep potentiates the negative inotropic effect of adenosine on guinea-pig atria by preventing both its accumulation by atrial tissue and degradation by deaminase.
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors; D004109:Dilazep / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D013997:Time Factors
D001381:Azepines; D000243:Adenosine Deaminase; D004109:Dilazep; D000241:Adenosine; D002118:Calcium