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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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References

  1. Appleman, M. M., Thompson, W. J., Russell, T. R.: Cyclic nucleotide phosphodiesterase. In: Advances in cyclic nucleotide research, Vol. 3 (P. Greengard and G. Robinson, eds.), pp. 65–98 New York: Raven Press 1973

    Google Scholar 

  2. Berne, R. M.: Cardiac nucleotides in hypoxia: Possible role in regulation of coronary blood flow. Amer. J. Physiol.204, 317–322 (1963)

    Google Scholar 

  3. Bünger, R., Haddy, F. J., Querengässer, A., Gerlach, E.: An isolated guinea pig heart preparation with in vivo like features. Pflügers Arch.353, 317–326 (1975)

    Google Scholar 

  4. Gerlach, E., Deuticke, B., Dierkesmann, R.: Vergleichende Untersuchungen über die Bildung von Adenosin im Myocard verschiedener Tierspecies bei Sauerstoffmangel. Klin. Wschr.44, 1307–1310 (1966)

    Google Scholar 

  5. Gerlach, E., Deuticke, B., Dreisbach, R. H.: Der Nucleotid-Abbau im Herzmuskel bei Sauerstoffmangel und seine mögliche Bedeutung für die Coronardurchblutung. Naturwissenschaften50, 228–229 (1963)

    Google Scholar 

  6. Gerlach, E., Deuticke, B., Dreisbach, R. H., Rosarius, C. W.: Zum Verhalten von Nucleosiden und ihren dephosphorylierten Abbauprodukten in der Niere bei Ischämie und kurzzeitiger post-ischämischer Wiederdurchblutung. Pflügers Arch. ges. Physiol.278, 296–315 (1963)

    Google Scholar 

  7. Gilman, A. G.: A protein-binding assay for adenosine 3′5′-cyclic monophosphate. Proc. nat. Acad. Sci. (Wash.)67, 305–312 (1970)

    Google Scholar 

  8. Gudbjarnason, S., Mathes, P., Ravens, K. G.: Functional compartmentation of ATP and creatine phosphate in the heart muscle. J. Mol. Cell. Cardiol.1, 325–339 (1970)

    Google Scholar 

  9. Imai, S., Riley, A. L., Berne, R. M.: Effect of ischemia on adenine nucleotides in cardiac and skeletal muscle. Circulat. Res.15, 443–450 (1964)

    Google Scholar 

  10. Kalckar, H. M.: Differential spectrophotometry of purine compounds by means of specific enzymes. I. Determination of hydroxypurine compounds. J. biol. Chem.167, 429–443 (1947a)

    Google Scholar 

  11. Kalckar, H. M.: Differential spectrophotometry of purine compounds by means of specific enzymes. II. Determination of adenine compounds J. biol. Chem.167, 445–459 (1947b)

    Google Scholar 

  12. Kübler, W., Spieckermann, P. G., Bretschneider, H. J.: Influence of dipyridamol on myocardial adenosine metabolism. J. Mol. Cell. Cardiol.1, 23–38 (1970)

    Google Scholar 

  13. Liu, M. S., Feinberg, H.: Incorporation of adenosine 8-14C and inosine 8-14C into rabbit heart adenine nucleotides. Amer. J. Physiol.220, 1242–1248 (1971)

    Google Scholar 

  14. Olsson, R. A.: Changes in content of purine nucleoside i canine myocardium during coronary occlusion. Circulat. Res.26, 301–306 (1970)

    Google Scholar 

  15. Polimeni, P. I.: Extracellular space and ionic distribution in rat ventricle. Amer. J. Physiol.227, 676–683 (1974)

    Google Scholar 

  16. Rubio, R., Berne, R. M.: Release of adenosine by the normal myocardium in dogs and its relationship to the regulation of coronary resistance. Circulat. Res.25, 407–415 (1969)

    Google Scholar 

  17. Rubio, R., Berne, R. M., Dobson, J. R.: Sites of adenosine production in cardiac and skeletal muscle. Amer. J. Physiol.225, 938–953 (1973)

    Google Scholar 

  18. Rubio, R., Wiedmeier, V. Th., berne, R. M.: Nucleoside phosphorylase: localisation and role in the myocardial distribution of purines. Amer. J. Physiol.222, 550–555 (1972)

    Google Scholar 

  19. Schultz, G., Böhme, E., Hardman, J. G.: Separation and purification of cyclic nucleotides by ion-exchange resin column chromatography. In: Methods in Enzymology, Vol. 38: Hormone action, Part C, Cyclic Nucleotides (J. G. Hardman and B. W. O'Malley, eds.), pp. 9–20. New York: Academic Press 1974

    Google Scholar 

  20. Schulze, W., Krause, E. G., Wollenberger, A.: Cytochemical demonstration and localisation of adenyl cyclase in skeletal and cardiac muscle. In: Advances in cyclic nucleotide research, Vol. I (P. Greengard and G. Robinson, eds.), pp. 249–260. New York, Raven Press 1972

    Google Scholar 

  21. Shimizu, H., Daly, J. W., Creveling, C. R.: A radioisotopic method for measuring the formation of adenosine 3′5′-cyclic monophosphate in incubated slices of brain. J. Neurochem.16, 1609–1619 (1969)

    Google Scholar 

  22. Tsuboi, K. K., Price, T. D.: Isolation, detection and measure of microgram quantities of labeled tissue nucleotides. Arch. Biochem. Biophys.81, 223–237 (1959)

    Google Scholar 

  23. Wiedmeier, V. Th., Rubio, R., Berne, R. M.: Incorporation and turnover of adenosine-U-14C in perfused guinea pig myocardium. Amer. J. Physiol.223, 51–54 (1972)

    Google Scholar 

  24. Yagi, K., Mase, R.: Possible compartmentation of adenine nucleotides in a coupled reaction system composed of F-actomyosin-adenosinetriphosphatase and creatine kinase. In: Molecular Biology of Muscular Biology of Muscular Contraction (S. Ebashi, F. Oosawa, T. Sekine and Y. Tonomura, eds.), pp. 109–123. Amsterdam: Elsevier Publishing Co. 1965

    Google Scholar 

  25. Zilversmit, D. B., Entman, C., Fishler, M. C.: On the calculation of “turnover time” and “turnover rate” from experiments involving use of labeling agents. J. gen. Physiol.26, 325–331 (1943)

    Google Scholar 

  26. Zimmer H.-G., Trendelenburg, Chr., Kammermeier, H., Gerlach, E.: De novo synthesis of myocardial adenine nucleotides in the rat. Circulat. Res.32, 635–642 (1973)

    Google Scholar 

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  1. Physiologisches Institut der Universität München, Pettenkoferstrasse 12, D-8000, München 2, Germany

    Jürgen Schrader & Eckehart Gerlach

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  1. Jürgen Schrader
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  2. Eckehart Gerlach
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Additional information

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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  • DOI: https://doi.org/10.1007/BF00585148

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