@entity859 mediates the negative chronotropic action of adenosine 5'-triphosphate in the XXXX sinus node.

@entity1 @entity4485 @entity859 @entity845 @entity3416 @entity235 @entity33268 @entity855
@entity855 exerts pronounced electrophysiologic effects in the @entity1 heart. The present study tested the hypothesis that the negative chronotropic action of @entity855 in the @entity235 sinus node is dependent on its degradation to @entity859 . Increasing doses of the following compounds were administered in the sinus nodal artery of 12 open chest @entity235 (either sex, 30-35 kg) anesthetized with @entity4485 (30 mg/kg i.v.): @entity859 , @entity855 , alpha,beta @entity845 - @entity855 (AMPCPP) and beta,gamma @entity845 - @entity855 ( @entity33268 ). 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 @entity859 greater than or equal to @entity855 greater than or equal to @entity33268 much greater than AMPCPP = 0. In 3 of 12 @entity235 the emergence of junctional escape rhythm was observed after the highest dose of either @entity859 , @entity855 or @entity33268 . In addition, @entity3416 , a selective competitive inhibitor of @entity859 at P1-purinoceptor site, reduced the effects of maximal doses of @entity859 , @entity855 and @entity33268 by 52 +/- 7, 67 +/- 8 and 72 +/- 6%, respectively (each, P less than .05; @entity33268 vs. @entity859 , P less than .05). The present data indicate that the negative chronotropic action of @entity855 is due to its rapid catabolism to @entity859 and the action of @entity859 at P1-purinoceptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)
