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 Langendroff-perfused rat heart models which differ particularly in inorganic phosphate (Pi) 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 microM) 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 Pi in the anoxic heart (Chen W, et al., 1996). We discuss the physiological significance of this heart-specific duality of degradation pathways.
Chen
W
W
Groupe de Biophysique de l'Ecole Polytechnique et de l'URA D1254 du CNRS, Ecole Polytechnique, Palaiseau, France.
Guéron
M
M
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000502:physiology*; D058892:Adenosine Deaminase Inhibitors; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000378:metabolism / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D006439:Hemodynamics; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007291:Inosine Monophosphate / Q000502:physiology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D010710:Phosphates / Q000032:analysis; D011684:Purine Nucleosides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D058892:Adenosine Deaminase Inhibitors; D000963:Antimetabolites; D004791:Enzyme Inhibitors; D010710:Phosphates; D011684:Purine Nucleosides; D007291:Inosine Monophosphate; D000249:Adenosine Monophosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; D003847:Deoxyglucose; D000243:Adenosine Deaminase; D000225:Adenine