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Ischemia Related Changes in Adenine Nucleotide Metabolism

  • N. Murakami
  • W. D. Lust
  • F. A. M. de Azeredo
  • J. V. Passonneau

Abstract

Derangements in the concentrations of the adenine nucleotides are a common occurrence during and after an ischemic episode. ATP levels decrease rapidly at the onset of ischemia and remain depressed for the entire period of ischemia (12, 24). Upon recirculation of the tissue, the extent of ATP restoration depends on the duration of the ischemic insult. For example, the ATP levels were completely regenerated at 60 min of recirculation following 1 and 5 min of bilateral occlusion, but not after 20 and 60 min (16). The total adenylates (sum of ATP + ADP + AMP) decrease somewhat more slowly during ischemia; in decapitated mouse forebrains, the half-time for the disappearance of total adenylates was approximately 32 min. The total adenylates were also very slow to recover. Ljunggren et al. (10) reported that the levels were significantly less than control at 3 hours after a 3 min ischemic interval. Since the hydrolysis of ATP is the major source of energy for a host of biochemical processes, alterations in adenine nucleotide metabolism resulting from ischemia could have pronounced effects on brain function and therefore on the likelihood of survival after ischemia.

Keywords

Brain Slice Cyclic Nucleotide Adenine Nucleotide Mongolian Gerbil Ischemic Episode 
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References

  1. 1.
    Daly, J.W. (1976): The nature of receptors regulating the formation of cyclic AMP in brain slices. Life Sciences 18: 1349–1358.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferrendelli, J.A., Gross, R.A., Kinscherf, D.A. and Rubin, E.H. (1979): Effects of seizures and anti-convulsant drugs on cyclic nucleotide regulation in the CNS. In: “Neuropharmacology of Cyclic Nucleotides,” G.C. Palmer, ed., pp. 211–227, Urban & Schwarzenberg, Baltimore.Google Scholar
  3. 3.
    Gottstein, U. and Paulson, O.B. (1972): The effect of intracarotid aminophylline infusion on cerebral circulation. Stroke 3: 560–565.PubMedCrossRefGoogle Scholar
  4. 4.
    Harper, J.F. and Brooker, G. (1975): Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2’0 acetylation by acetic anhdride in aqueous solution. J. Cyclic Nucleot. Res. 1: 207–218.Google Scholar
  5. 5.
    Ito, U., Spatz, M., Walker, J.T. and Klatzo, I. (1975): Experimental cerebral ischemia in mongolian gerbils. Acta Neuropath. ( Berl. ) 32: 209–223.CrossRefGoogle Scholar
  6. 6.
    Jones, D.J. and Stavinoha, W.B. (1977): Levels of cyclic nucleotides in mouse regional brain following 300 cosec microwave irradiation. J. Neurochem. 28: 759–763.PubMedCrossRefGoogle Scholar
  7. 7.
    Kerr, S.E. (1935): Studies on the phosphorus compounds of the brain. I. Phosphocreatine. J. Biol. Chem. 110: 625–635.Google Scholar
  8. 8.
    Kleihues, P., Kobayashi, K. and Hossmann, K.-A. (1974): Purine nucleotide metabolism in the cat brain after 1 hour of complete ischemia. J. Neurochem. 23: 417–425.PubMedCrossRefGoogle Scholar
  9. 9.
    Kobayashi, M., Lust, W.D. and Passonneau, J.V. (1977): Concentration of energy metabolites and cyclic nucleotides during and after bilateral ischemia in the gerbil cerebral cortex. J. Neurochem. 29: 53–59.PubMedCrossRefGoogle Scholar
  10. 10.
    Ljunggren, B., Ratcheson, R.A. and Siesjo, B.K. (1974): Cerebral metabolic state following complete compression ischemia. Brain Res. 73: 291–307.PubMedCrossRefGoogle Scholar
  11. 11.
    Lowry, O.H. and Passonneau, J.V. (1972): A Flexible System of Enzymatic Analysis. Academic Press, New York.Google Scholar
  12. 12.
    Lust, W.D., Mrsulja, B.E., Mrsulja, B.J., Passonneau, J.V. and Klatzo, I. (1975): Putative neurotransmitters and cyclic nucleotides in prolonged ischemia of the cerebral cortex. Brain Res. 98: 394–399.PubMedCrossRefGoogle Scholar
  13. 13.
    Mrsulja, B.B., Lust, W.D., Mrsulja, B.J., Passonneau, J.V. and Klatzo, I. (1976): Post-ischemic changes in certain metabolites following prolonged ischemia in the gerbil cerebral cortex. J. Neurochem. 26: 1099–1103.CrossRefGoogle Scholar
  14. 14.
    Mrsulja, B.B., Mrsulja, B.J., Ito, U., Walker, J.T., Spatz, M. and Klatzo, I. (1975): Experimental cerebral ischemia in mongolian gerbils. II. Changes in carbohydrates. Acta Neuropath. ( Berl. ) 33: 91–103.CrossRefGoogle Scholar
  15. 15.
    Murakami, N., Lust, W.D., Wheaton, A.B. and Passonneau, J.V. (1979): Short-term unilateral ischemia in gerbils: a reevaluation. In: ‘Pathophysiology of Cerebral Energy Metabolism,“ B.B. Mrsulja, L. M. Rakic, I. Klatzo and M. Spatz, eds., pp. 33–46, Plenum Press, New York.CrossRefGoogle Scholar
  16. 16.
    Passonneau, J.V., Kobayashi, M. and Lust, W.D. (1977): The effect of bilateral ischemia and recirculation on energy reserves and cyclic nucleotides in the cerebral cortex of gerbils. In: “Alcohol and Aldehyde Metabolizing Systems,” R.G. Thurman, J.R. Williamson, H.R. Drott and B. Chance, eds., v 3: pp. 485–498, Academic Press, New York.Google Scholar
  17. 17.
    Phillis, J.W. and Kostopoulous, G.K. (1975): Adenosine as a putative neurotransmitter in the cerebral cortex. Studies with potentiators and antagonists. Life Sciences 17: 1085–1094.PubMedCrossRefGoogle Scholar
  18. 18.
    Ponten, U., Ratcheson, R.S., Salford, L.G. and Siesjo, B.K. (1973): Optimal freezing conditions for cerebral metabolites in rats. J. Neurochem. 21: 1127–1138.PubMedCrossRefGoogle Scholar
  19. 19.
    Nordstrom, D.-H, Rehncrona, S. and Siesjo, B.K. (1978): Restitution of cerebral energy state as well as of glycolytic metabolites, citric acid cycle intermediates and associated amino acids after 30 minutes of complete ischemia in rats anesthetized with nitrous oxide or phenobarbital. J. Neurochem. 30: 479–486.PubMedCrossRefGoogle Scholar
  20. 20.
    Nordstom, C.-H., Rehncrona, S., Siesjo, B.K. and Westerberg, E. (1077): Adenosine in rat cerebral cortex: Its determination, normal values and correlation to AMP and cyclic AMP during shortlasting ischemia. Acta Physiol. Scand. 101: 63–71.CrossRefGoogle Scholar
  21. 21.
    Sattin, A. (1971): Increase in the content of adenosine 3’,5’-monophosphate in mouse forebrain during seizures and prevention of the increase by methylxanthines. J. Neurochem. 18: 1087–1096.PubMedCrossRefGoogle Scholar
  22. 22.
    Sattin, A. and Rall, T.W. (1970): The effect of adenosine and adenine nucleotides on the cyclic adenosine 3’,5’-phosphate content of guinea pig cerebral cortex slices. Mol. Pharmacol. 6: 13–23.PubMedGoogle Scholar
  23. 23.
    Steiner, A.L., Wehmann, R.E., Parker, C.W. and Kipnis, D.M. (1972): Radioimmunoassay for cyclic nucleotides. J. Biol. Chem. 247: 1121–1124.PubMedGoogle Scholar
  24. 24.
    Watanabe, H. and Ishii, S. (1976): The effect of brain ischemia on the levels of cyclic AMP and glycogen metabolism in gerbil brain in vivo. Brain Res. 102: 385–389.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • N. Murakami
    • 1
  • W. D. Lust
    • 1
  • F. A. M. de Azeredo
    • 1
  • J. V. Passonneau
    • 1
  1. 1.Laboratory of Neurochemistry National Institute of Neurological and Communicative Disorders and StrokeNational Institutes of HealthBethesdaUSA

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