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Molecular and Cellular Biochemistry

, Volume 244, Issue 1–2, pp 125–128 | Cite as

Effect of caffeine on metabolism of L-arginine in the brain

  • Jelenka Nikolic
  • Gordana Bjelakovic
  • Ivana Stojanovic
Article

Abstract

Methylxanthines are widely consumed because of their stimulating effect primarily on the central nervous system. Their diuretic and respiratory stimulant action is used in clinical medicine. L-Arginine metabolism in the brain is very important for normal brain function. In addition to brain protein synthesis, arginine is a substrate for the production of urea, creatine, nitric oxide, agmatine, glutamic acid, ornithine, proline and polyamines. As known, many of these compounds are very important in brain function. There is no information relating to effects of caffeine on arginine metabolism in the brain, however, there is a lot of new information about arginine metabolism and caffeine action on the central nervous system. So, we have hypothesized the existence of a relationship that may be of interest in understanding mechanisms of caffeine effects on the central nervous system that may have utility in the clinical applications.

In our experiment protocol we used male Wistar rats weighing about 200 g. Caffeine was added to the drinking water in gradually increasing amounts, from 2 g/l over the first 3 days, to 4 g/l over the last 7 days. A control group was given drinking water without caffeine. The level of lipid peroxidation, arginase and diamine oxidase (DAO) activity in the brain was measured. The results of our study show that arginase and diamine oxidase were decreased in animals treated with caffeine. The level of lipid peroxidation (MDA) was decreased also.

The inhibitory effect of caffeine on arginase activity indicates that caffeine provides more arginine for consumption in other metabolic pathways. Considering the central stimulant effects of caffeine and the decreased lipid peroxidation level, it can be assumed that moderate short-term consumption of caffeine may be beneficial for brain function.

caffeine arginase brain lipid peroxidation polyamines diamine oxidase 

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References

  1. 1.
    Curatolo PW, Robertson D: The health consequences of caffeine. Ann Intern Med 98: 641-653, 1983Google Scholar
  2. 2.
    Barbier A: Caffeine protects against Parkinson's disease? Trends Pharmacol Sci 22: 500, 2001Google Scholar
  3. 3.
    Kaiser SM, Quinn RJ: Adenosine receptors as potential therapeutic targets. Drug Discovery Today 4: 542-551, 1999Google Scholar
  4. 4.
    Wu G, Morris SM Jr: Arginine metabolism: Nitric oxide and beyond. Biochem J 336: 1-17, 1998Google Scholar
  5. 5.
    Herzfeld A, Raper S: The heterogenity of arginase in rat tissues. Biochem J 153: 469-478, 1976Google Scholar
  6. 6.
    Wiesinger H: Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 64: 365-391, 2001Google Scholar
  7. 7.
    Farrer I, Costell M, Grisolia S: Lesch-Nyhan syndrome-like behavior in rats from caffeine ingestion. FEBS Lett 141: 275-278, 1982Google Scholar
  8. 8.
    Minana D, Portoles M, Jorda A, Grisolia S: Lesch-Nyhan syndrome, Caffeine model: Increase of purine and pyrimidine enzymes in rat brain. J Neurochem 43: 1556-1560, 1984Google Scholar
  9. 9.
    Porembska Z, Kedra M: Early diagnosis of myocardial infarction by arginase determination. Clin Chim Acta 60: 555-561, 1975Google Scholar
  10. 10.
    Stroev EA, Makarova VG: In: Laboratory Manual in Biochemistry. Mir, Moscov, 1989, pp 251-255Google Scholar
  11. 11.
    Bashrach U, Reches B: Enzymic assay for spermine and spermidine. Anal Biochem 17: 38-48, 1966Google Scholar
  12. 12.
    Lowry OHR, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with Folin phenol reagent. J Biol Chem 193: 265-275, 1951Google Scholar
  13. 13.
    Mimic-Oka J, Cupic Z, Japundzic I: Effect of adrenal function on level of hepatic and extrahepatic arginase. Experientia 27: 1477-1478, 1971Google Scholar
  14. 14.
    Fredholm BB: On the mechanism of action of theophylline and caffeine. Acta Med Scand 217: 149-153, 1985Google Scholar
  15. 15.
    Nahorski SR, Rogers KJ: Inhibition of 3′,5′-nucleotide phosphodiesterse and the stimulation of cerebral cyclic AMP formation by biogenic amines in vitro and in vivo. Neuropharmacology 15: 609-612, 1976Google Scholar
  16. 16.
    Bellet S, Kostis J, Roman L, DeCastro O: Effect of coffee ingestion on adrenocortical secretion in young men and dogs. Metabolism 18: 1007-1012, 1969Google Scholar
  17. 17.
    Fredholm BB: Adenosine actions and adenosine receptors after one-week treatment with caffeine. Acta Physiol Scand 115: 283-286, 1982Google Scholar
  18. 18.
    Rosenfeld JL, Duta SD, Chedda GB, Tritsch GL: Purine and pyrimidine inhibitors of arginase. Biochem Biophys Acta 410: 164-166, 1975Google Scholar
  19. 19.
    Reddy PUM, Ramana Rao JV: Inhibition of arginase in sheep brain homogenates by some L-amino acids. Experientia 37: 814, 1981Google Scholar
  20. 20.
    Byus CV, Russell DH: Ornithine decarboxylase activity: Control by cyclic nucleotides. Science 187: 650-652, 1975Google Scholar
  21. 21.
    Colombatto S, Fasulo L, Mondardini A, Nmalabaila A, Grillo MA: Effect of caffeine on ornithine metabolism in rat brain, liver and kidney. Ital J Biochem 38: 75-82, 1989Google Scholar
  22. 22.
    Krycevskaya AA, Shugaley VS, Tsvetnenko EZ: Brain and liver arginase and polyamines in the mechanism of arginine protective effect under hypoxia. Bilt Exp Biol Med 4: 445-447, 1981Google Scholar
  23. 23.
    Lee C: Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin Chim Acta 295: 141-154, 2000Google Scholar
  24. 24.
    Devasagaya TP, Kamat JP, Mohan H, Kesavan PC: Caffeine as an oxidant: Inhibition of lipid peroxidation induced by reactive oxygen species. Biochim Biophys Acta 1282: 63-70, 1996Google Scholar
  25. 25.
    Wu G, Meininger CJ: Arginine nutrition and cardiovascular function. J Nutr 130: 2626-2629, 2000Google Scholar
  26. 26.
    Nikolic J: Alcoholic intoxication. In: G.A. Qureshi et al. (eds). Neurochemical Markers of Degenerative Nervous Diseases and Drug Addiction. VSP, 1998, pp 193-221Google Scholar
  27. 27.
    De Mendoca A, Sebastiao AM, Ribeiro JA: Adenosine: Does it have a neuroprotective role after all? Brain Res Rev 33: 258-274, 2001Google Scholar
  28. 28.
    Essayan DM: Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol 57: 965-973, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Jelenka Nikolic
    • 1
  • Gordana Bjelakovic
    • 1
  • Ivana Stojanovic
    • 1
  1. 1.Institute of Biochemistry, Faculty of MedicineUniversity of NisNisYugoslavia

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