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Compartmentation of cardiac adenine nucleotides and formation of adenosine

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Summary

After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either14C-adenine or14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3′5′-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substance. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart.

Our findings provide evidence that at least two different adenine nucleotide compartments of the heart serve as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.

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A preliminary report of part of this work appeared in “Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarction” Vol. 7 of “Recent advances in studies on cardiac structure and metabolism”. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976

A preliminary report of part of this work appeared in “Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarction” Vol. 7 of “Recent advances in studies on cardiac structure and metabolism”. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976

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Schrader, J., Gerlach, E. Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pflugers Arch. 367, 129–135 (1976). https://doi.org/10.1007/BF00585148

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Key words

  • 14C-adenine
  • Salvage of purine nucleosides and bases
  • Isolated perfused guinea pig heart
  • Cyclic 3′5′-AMP
  • Inosine
  • Hypoxanthine