Inosine incorporation into myocardial nucleotides

Abstract

Inosine and hypoxanthine, degradative products of adenine nucleotides are released and also taken up by the heart. In order to determine whether inosine can be incorporated into adenine nucleotides by direct phosphorylation or whether initial degradation to hypoxanthine is necessary, isolated guinea pig hearts were perfused with non-recirculating Krebs-Henseleit solution containing uniformly labeled inosine (0.004 μ m) or 8-[ 14C]-hypoxanthine (0.01 μ m). Enzymic hydrolysis of the adenine nucleotides from hearts perfused with inosine revealed that only the base moiety of the nucleosides was labeled, indicating that inosine was degraded to hypoxanthine prior to incorporation. Analysis of perfusates for labeled inosine and hypoxanthine indicated interconversion of these compounds by nucleoside phosphorylase which is known to be present in endothelial cells and pericytes. The reduction of the specific activity of inosine and hypoxanthine that passed through the coronary vascular bed was greater than could be accounted for by the unlabeled endogenous inosine and hypoxanthine released from the myocardium, and indicates exchange of the exogenous labeled compounds with the endogenous pool of inosine and hypoxanthine in the interstitial fluid and intracellular compartments.