AMP DEGRADATION IN THE PERFUSED RAT-HEART DURING 2-DEOXY-D-GLUCOSE PERFUSION AND ANOXIA .2. THE DETERMINATION OF THE DEGRADATION PATHWAYS USING AN ADENOSINE-DEAMINASE INHIBITOR

Using the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), we determine the contribution of the adenosine pathway to the abundant purine release of two Langendorff-perfused rat heart models which differ particularly in inorganic phosphate (P-i) content: the 2-deoxy-D-glucose (2DG) perfused heart and the anoxic heart. We m easure the release of coronary purines by high performance liquid chro matography, and the content of myocardial metabolites by P-31 nuclear magnetic resonance spectroscopy. In the 2DG-perfused heart (2 mM for 4 5 min), the release of inosine [130 nmol/(min . gww)] is much larger t han that of adenosine, and EHNA (50 mu M) has little effect, showing t hat the pathway of inosine monophosphate (IMP) accounts for 97% of pur ine catabolism. In the anoxic heart (100% N-2 for 45 min), where inosi ne and adenosine release are comparable in the absence of EHNA, the in hibitor reduces the release of inosine and catabolites from 50 to 20 n mol/(min . gww) and increases that of adenosine [from 30 to 55 nmol/(m in . gww)], showing that the contributions of the IMP and adenosine pa thways are 23 and 77%. The difference between the two models has been ascribed to the inhibition of AMP deaminase by P-i in the anoxic heart (Chen W, et al., 1996). We discuss the physiological significance of this heart-specific duality of degradation pathways. (C) 1996 Academic Press Limited