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

Weina Chen, Maurice Guéron

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21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2175-2182
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number10
DOIs
StatePublished - Oct 1996

Fingerprint

Adenosine Deaminase Inhibitors
Deoxyglucose
Adenosine Monophosphate
Adenosine
Perfusion
Inosine
Inosine Monophosphate
AMP Deaminase
Purines
Hypoxia
Magnetic Resonance Spectroscopy
Phosphates
High Pressure Liquid Chromatography
9-(2-hydroxy-3-nonyl)adenine

Keywords

  • 2-deoxy-D-glucose
  • Adenosine deaminase
  • AMP deaminase
  • Anoxia
  • EHNA
  • Isolated rat heart
  • NMR

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "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",
abstract = "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.",
keywords = "2-deoxy-D-glucose, Adenosine deaminase, AMP deaminase, Anoxia, EHNA, Isolated rat heart, NMR",
author = "Weina Chen and Maurice Gu{\'e}ron",
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T2 - The determination of the degradation pathways using an adenosine deaminase inhibitor

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AU - Guéron, Maurice

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N2 - 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.

AB - 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.

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