Comparison of the adenine nucleotide metabolism of dog atrial and ventricular myocardium

Abstract

Measurements of atrial and ventricular adenine nucleotides, nucleosides and bases in dog heart indicated that normal atrial ATP, ADP and AMP levels are about one-half those of normal ventricular tissue, but atrial and ventricular tissue levels of adenosine, inosine, and hypoxanthine were about equal. With ischemia, production of adenosine and inosine was less in atrial than in ventricular muscle. In the ventricle, 5′-nucleotidase is associated with external membranes, including those of the T-tubular system and the lack of a T-tubular network in atrium suggested that there might be fewer AMP hydrolyzing sites and hence a slower rate of adenosine production in response to ischemia. This possibility was ruled out since measurements of 5′-nucleotidase on crude tissue extracts indicated that atrial tissue has 2 to 3 times the activity of ventricular tissue. Furthermore, measurements of adenosine kinase activity indicate that atrial and ventricular activities of this enzyme are about equal; hence the lower adenosine levels in atria are also not due to a higher rate of adenosine rephosphorylation. Inhibition of 5′-nucleotidase by ATP and ADP can also be eliminated as a cause of the differences in atrial and ventricular adenosine formation since the concentrations of these compounds are lower in atrial than in ventricular muscle. Finally, the lower levels of IMP and inosine in atrial tissue indicate that deamination by adenylate deaminase is not the major pathway for AMP degradation in atrial tissue. It is possible that the lower substrate (AMP) concentration for 5′-nucleotidase is responsible for the lower adenosine production by atrial tissue in response to ischemia. However, to what extent this contributed to the lower atrial adenosine levels cannot be determined from these data.