Neurochemical Research

, Volume 4, Issue 2, pp 277–287 | Cite as

Effect of administration of 5-hydroxytryptophan and an inhibitor ofl-aromatic amino acid decarboxylase on glucose metabolism in rat brain

  • Kar-Lit Wong
  • Gertrude M. Tyce
Original Articles

Abstract

The effect of 5-hydroxytryptophan (5-HTP)—the precursor of serotonin (5-hydroxytryptamine, 5-HT)—and of an inhibitor,N-(dl-seryl)-N′-(2,3,4-trihydroxybenzyl)hydrazine (Ro4-4602), ofl-aromatic amino acid decarboxylase on the metabolism of glucose to amino acids in brain tissue was investigated. Labeled glucose (20 μCi, 0.24 mg in 0.2 ml 0.9% saline) was injected intravenously into fed rats pretreated with Ro4-4602 (50 mg/kg intraperitoneally) either alone or in combination with 5-HTP (30 mg/kg intravenously) or with the appropriate vehicle. After the injection of Ro4-4602 plus 5-HTP, the concentrations of 5-HT and 5-HTP in brain were increased, but the increase of 5-HTP that Ro4-4602 slightly inhibits the reaction of decarboxylation in the brain, although at the dose used the drug is usually considered to act only peripherally. After administration of Ro4-4602 alone or combined with 5-HTP, the concentration of glucose in plasma was not significantly increased. However, the concentration of glucose in brain was markedly increased with such treatments. The administration of Ro4-4602 alone or combined with 5-HTP reduced the flux of14C from labeled glucose to amino acids in brain. The concentrations of amino acids in brain were little changed by these treatments.

Keywords

Glucose Brain Tissue Glucose Metabolism Hydrazine Acid Decarboxylase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bachelard, H. S., Gaitonde, M. K., andVrba, R., 1966. The effect of psychotropic drugs on the utilization of glucose carbon atoms in the brain, heart and liver of the rat. Biochem. Pharmacol. 15:1039–1043.PubMedGoogle Scholar
  2. 2.
    Berson, S. A., Weisenfeld, S., andPascullo, M. 1959. Utilization of glucose in normal and diabetic rabbits: Effects of insulin, glucagon and glucose. Diabetes 8:116–127.PubMedGoogle Scholar
  3. 3.
    Flock, E. V., Tyce, G. M., andOwen, C. A., Jr., 1970. Effects of ethanol on glucose utilization in rat brain. Proc. Soc. Exp. Biol. Med., 135:325–333.PubMedGoogle Scholar
  4. 4.
    Tyce, G. M., Flock, E. V., andOwen, C. A., Jr. 1971. Metabolism of glucose in brain after hepatectomy. Exp. Biol. Med. 4:92–103.PubMedGoogle Scholar
  5. 5.
    Flock, E. V., Tyce, G. M. andOwen, C. A., Jr. 1966. Utilization of [U-14C]glucose in brain after total hepatectomy in the rat. J. Neurochem. 13:1389–1406.PubMedGoogle Scholar
  6. 6.
    Cremer, J. E. 1970. Selective inhibition of glucose oxidation by triethyltin in rat brain in vivo. Biochem. J. 119:95–102.PubMedGoogle Scholar
  7. 7.
    Gaitonde, M. K. andRichter, D. 1966. Changes with age in the utilization of glucose carbon in liver and brain. J. Neurochem. 13:1309–1316.PubMedGoogle Scholar
  8. 8.
    Otsuki, S., Watanabe, S., Ninomiya, K., Hoaki, T., andOkumura, N. 1968. Correlation between [U-14C]glucose metabolism and function in perfused cat brain. J. Neurochem., 15:859–865.Google Scholar
  9. 9.
    Wong, K. L., andTyce, G. M. 1978. Effect of the administration ofl-5-hydroxytryptophan and a monoamine oxidase inhibitor on glucose metabolism in rat brain. J Neurochem. 31:613–620.PubMedGoogle Scholar
  10. 10.
    Bartholini, G., Burkard, W. P., Pletscher, A., andBates, H. M. 1967. Increase of cerebral catecholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature 215:852–853.Google Scholar
  11. 11.
    Matussek, N., Angst, J., Benkert, O., Gmür, M., Papousek, M., Rüther, E., andWoggon, B. 1974. The effect ofl-5-hydroxytryptophan alone and in combination with a decarboxylase inhibitor (Ro4-4602) in depressive patients. Adv. Biochem. Psychopharmacol. 11:399–404.PubMedGoogle Scholar
  12. 12.
    Van Woert, M. H., Rosenbaum, R., Howieson, J., andBowers, M. S. 1977. Long-term therapy of myoclonus and other neurologic disorders withl-5-hydroxytryptophan and carbidopa. N. Engl. J. Med. 296:70–75.PubMedGoogle Scholar
  13. 13.
    Chadwick, D., Hallett, M., Harris, R., Jenner, P., Reynolds, E. H., andMarsden, C. D. 1977. Clinical, biochemical, and physiological features distinguishing myoclonus responsive to 5-hydroxytryptophan, tryptophan with a monoamine oxidase inhibitor, and clonazepam. Brain 100:455–487.PubMedGoogle Scholar
  14. 14.
    Campanella, G., Algeri, S., Cerletti, C., Dolfini, E., Jori, A., andRinaldi, F. 1977. Correlation of clinical symptoms, HVA and 5-HIAA in CSF and plasmal-dopa in parkinsonian patients treated withl-dopa andl-dopa+Ro4-4602. Eur. J. Clin. Pharmacol. 11:255–261.PubMedGoogle Scholar
  15. 15.
    Meyer, J. S., Welch, K. M. A., Deshmukh, V. D., Perez, F. I., Jacob, R. H., Haufrect, D. B., Mathew, N. T., andMorrell, R. M. 1977. Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. J. Am. Geriatr. Soc. 25:289–298.PubMedGoogle Scholar
  16. 16.
    Lovenberg, S., andEngelman, K. 1971. Assay of serotinin, related metabolites and enzymes. Suppl. vol. Pages 1–34,in Glick, D. (ed.), Methods of Biochemical Analysis, Interscience, New York.Google Scholar
  17. 17.
    Veech, R. L., andHawkins, R. A. 1974. Brain-blowing, a technique for in vivo study of brain metabolism. Pages 171–182,in Marks, N., andRodnight, R. (eds.), Research Methods in Neurochemistry, Vol. 2, Plenum Press, New York.Google Scholar
  18. 18.
    Tyce, G. M. 1971. Effect of dihydroxyphenylalanine administered with a monoamine oxidase inhibitor on glucose metabolism in rat brain. Biochem. Pharmacol. 20:2371–2384.PubMedGoogle Scholar
  19. 19.
    Tyce, G. M., andOwen, C. A., Jr. 1973. The effect ofl-3,4-dihydroxyphenylalanine administration on glucose metabolism in brain. J. Neurochem., 20:1563–1573.PubMedGoogle Scholar
  20. 20.
    Slein, M. W. 1965.d-glucose: Determination with hexokinase and glucose-6-phosphate dehydrogenase. Pages 117–133,in Bergmeyer, H.-U. (ed.), Methods of Enzymatic Analysis, Academic Press, New York.Google Scholar
  21. 21.
    Flock, E. V., Tyce, G. M., andOwen, C. A., Jr. 1969. Glucose metabolism in brains of eviscerated rats with different blood levels of glucose. Mayo Clin. Proc. 44:387–405.PubMedGoogle Scholar
  22. 22.
    Tyce, G. M. 1976. The effect ofl-dopa and an inhibitor of peripheral decarboxylation on glucose metabolism in brain. J. Neurochem. 27:1397–1403.PubMedGoogle Scholar
  23. 23.
    Levine, R. A., Pesch, L. A., Klatskin, G., andGiarman, N. J. 1964. Effect of serotonin on glycogen metabolism in isolated rat liver. J. Clin. Invest. 43:797–809.PubMedGoogle Scholar
  24. 24.
    Woods, S. C., andPorte, D., Jr. 1974. Neural control of the endocrine pancreas. Physiol Rev. 54:596–619.PubMedGoogle Scholar
  25. 25.
    Oldendorf, W. H. 1971. Brain uptake in radiolabeled amino acids, amines, and hexoses after arterial injection. Am. J. Physiol. 221:1629–1639.PubMedGoogle Scholar
  26. 26.
    Yoshino, Y., andElliott, K. A. C. 1970. Incorporation of carbon atoms from glucose into free amino acids in brain under normal and altered conditions. Can. J. Biochem. 48:228–235.PubMedGoogle Scholar
  27. 27.
    Bachelard, H. S., andLindsay, J. R. 1966. Effects of neurotropic drugs on glucose metabolism in rat brain in vivo. Biochem. Pharmacol. 15:1053–1058.PubMedGoogle Scholar
  28. 28.
    Lindsay, J. R., andBachelard, H. S. 1966. Incorporation of14C from glucose into α-keto acids and amino acids in rat brain and liver in vivo. Biochem. Pharmacol. 15:1045–1052.PubMedGoogle Scholar
  29. 29.
    Sanders-Bush, E., Gallager, D. A., andSulser, F. 1974. On the mechanism of brain 5-hydroxytryptamine depletion byp-chloroamphetamine and related drugs and the specificity of their action. Adv. Biochem. Psychopharmacol. 10:185–205.PubMedGoogle Scholar
  30. 30.
    Jacobs, B. L. 1974. Evidence for the functional interaction of two central neurotransmitters. Psychopharmacologia 39:81–86.PubMedGoogle Scholar
  31. 31.
    Lehninger, A. L. 1975. Biochemisty: The Molecular Basis of Cell Structure and Function, 2nd ed., Worth, New York.Google Scholar
  32. 32.
    Santini, M., andBerl, S. 1972. Effects of reserpine and monoamine oxidase inhibition on the levels of amino acids in sensory ganglia, sympathetic ganglia and spinal cord. Brain Res. 47:167–176.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1979

Authors and Affiliations

  • Kar-Lit Wong
    • 1
  • Gertrude M. Tyce
    • 1
  1. 1.Mayo Clinic and Mayo FoundationRochester

Personalised recommendations