Levels of Purine, Kynurenine and Lipid Peroxidation Products in Patients with Inflammatory Bowel Disease

  • Caroline M. Forrest
  • Stuart R. Gould
  • L. Gail Darlington
  • Trevor W. Stone
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 527)

Abstract

The factors affecting gut activity in inflammatory bowel disease are unclear, but purines and kynurenines may be involved in the regulation of neuronal activity and therefore gut motility and secretion. We have measured the serum levels of these compounds in patients and in sex-and age-matched controls. Purines and kynurenines were analysed using HPLC. The levels of tryptophan and its metabolites 3hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid were unchanged in all patients. However, the levels of kynurenine and kynurenic acid were significantly elevated in patients with inflammatory bowel disease when compared to control subjects. There were no significant differences between patients and controls for any of the purines analysed or for neopterin. In the inflammatory bowel disease patients serum lipid peroxidation products were significantly elevated when compared to control subjects, suggesting the presence of increased oxidative stress consistent with inflammatory activity. The elevated level of kynurenic acid may represent either a compensatory response to elevated activation of enteric neurones, or a primary abnormality, which induces a compensatory increase in gut activity, but may indicate a role for kynurenine modulation of glutamate receptors in the symptoms of inflammatory bowel disease.

Keywords

HPLC Acetonitrile Adenosine Serotonin Neurol 

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References

  1. I.
    T.W. Stone, H.A. Simmonds, Purines: Basic and Clinical Aspects (Kluwer Press, Dordrecht, 1991).CrossRefGoogle Scholar
  2. 2.
    I.M. Coupar, D.L. Hancock, The adenosine agonist NECA inhibits intestinal secretion and peristalsis, J. Pharm. Pharmac. 46, 801–804 (1994).CrossRefGoogle Scholar
  3. 3.
    V.H. Hopker, M.J. Saf rey, G. Bumstock, Neurite outgrowth of striatal neurons in vitro: Involvement of purines in the growth-promoting effect of myenteric plexus explants, Intern. J. Develop . Neurosci. 14, 439–451 (1996).Google Scholar
  4. 4.
    F.L. Christoti, H. Zhang, J.G. Yu, J. Guzman, J. Xue, M. Kim, Y.Z. Wang, H.J. Cooke, Differential gene expression of adenosine Al, Ala, Alb, and A3 receptors in the human enteric nervous system, J. Comp. Neurol. 439, 46–64 (2001).CrossRefGoogle Scholar
  5. 5.
    T.W. Stone, The neuropharmacology of quinolinic and kynurenic acids, Pharmacol. Revs. 45, 309–379 (1993).Google Scholar
  6. 6.
    T.W. Stone, The development and therapeutic potential of kynurenic acid and kynurenine derivatives for CNS protection, Trends Pharmacol. Sci. 21, 149–154 (2000).PubMedCrossRefGoogle Scholar
  7. 7.
    T.W. Stone, Kynurenines in the CNS - from endogenous obscurity to therapeutic importance, Progr. Neurobiol. 64, 185–218 (2001).CrossRefGoogle Scholar
  8. 8.
    T.W. Stone, M.N. Perkins, Quinolinic acid: a potent endogenous excitant at NMDA receptors, Europ. J. Pharmacol. 72, 411–412 (1981).CrossRefGoogle Scholar
  9. 9.
    M.N. Perkins, T.W. Stone, An iontophoretic investigation of the action of convulsant kynurenines and their interaction with the endogenous excitant kynurenic acid, Brain Res. 247, 184–187 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    S.S. Gill, R.W. Mueller, P.F. McGuire, Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity, Toxicologic Pathol. 28, 277–284 (2000).CrossRefGoogle Scholar
  11. 11.
    T.M. Skerry, PG. Genever, Glutamate signalling in non-neuronal tissues, Trends Pharmacol. Sci. 22 174–181 (2001).PubMedCrossRefGoogle Scholar
  12. 12.
    H.E. Shannon, B.D. Sawyer, Glutamate receptors of the NMDA subtype in myenteric plexus of the guinea pig ileum, J. Pharmacol. Exp. Therap. 215, 518–523 (1989).Google Scholar
  13. 13.
    S. Luzzi, S. Zilletti, S. Franchi-Micheli, A.M. Gori, F. Moroni, Agonists, antagonists and modulators of excitatory amino acid receptors in the guinea-pig myenteric plexus, Brit. J. Pharmacol. 95,1271–1277 (1988).CrossRefGoogle Scholar
  14. 14.
    D. Fuchs, G. Weiss, G. Reibnegger, H. Wachter, The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases, Crit. Rev. Clin. Lab. Sci,29,307–341 (1992).Google Scholar
  15. 15.
    G. Judmaier, P. Meyersbach, G. Weiss, H. Wachter, G. Reibnegger, The role of neopterin in assessing disease activity in Crohn’s disease: classification and regression trees, Amer. J. Grutroentero/. 88, 706–71 I (1993).Google Scholar
  16. 16.
    D. Neiderwieser, D. Fuchs, A. Hausen, G..ludmaier, G. Reibnegger, H. Wachter, C. Huber, Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis, Imntunobiol. 170,320–326 (1985).CrossRefGoogle Scholar
  17. 17.
    B. Duclos, J.M. Reimund, J.M. Lang, G. Coumaros, P. Chamouard, L. Lehr, R. Baumann, C. Koehl, J.P. Weill, Mononuclear cell activation in Crohn’s disease. Evaluation using serum assay of neopterin and interleukin-2 soluble receptors, Gastroenterol. Gin. Biol. 14,22–27 (1990).Google Scholar
  18. 18.
    R.S. Walmsley, R.C.S. Ayres, R.E. Pounder, R.N. Allan, A simple clinical colitis activity index, Gut 43. 2x)32 (1998).CrossRefGoogle Scholar
  19. 19.
    R.F. Harvey, J.M. Bradshaw, A simple index of Crohn’s disease activity, Lancet I, 514 (1980).CrossRefGoogle Scholar
  20. 20.
    D.A. Drossman, An integrated approach to the irritable bowel syndrome, Aliment. Phnrrnncol. Iherap. 13 (sappl 2), 3–14 (1999).CrossRefGoogle Scholar
  21. 22.
    N.C. Danbolt, Glutamate uptake, Progr . Neurobiol . 65, 1–105 (2001).Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Caroline M. Forrest
  • Stuart R. Gould
  • L. Gail Darlington
  • Trevor W. Stone

There are no affiliations available

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