AMP degradation in the perfused rat heart during 2-deoxy-D-glucose perfusion and anoxia. Part II: 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 measure the release of coronary purines by high performance liquid chromatography, and the content of myocardial metabolites by ³¹P nuclear magnetic resonance spectroscopy. In the 2DG-perfused heart (2 mM for 45 min), the release of inosine [130 nmol/(min·gww)] is much larger than that of adenosine, and EHNA (50 μM) has little effect, showing that the pathway of inosine monophosphate (IMP) accounts for 97% of purine catabolism. In the anoxic heart (100% N₂ for 45 min), where inosine and adenosine release are comparable in the absence of EHNA, the inhibitor reduces the release of inosine and catabolites from 50 to 20 nmol/(min·gww) and increases that of adenosine [from 30 to 55 nmol/(min·gww)], showing that the contributions of the IMP and adenosine pathways 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. We discuss the physiological significance of this heart-specific duality of degradation pathways.