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Ornithine Decarboxylase and Polyamine Biosynthesis in Pancreatic Adaptation

  • Christian Löser
  • Ulrike Cleffmann
  • Frauke Alves
  • Ulrich R. Fölsch
  • Werner Creutzfeldt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)

Summary

This study was designed to investigate the role of ornithine decarb-oxylase (ODC) and polyamines in pancreatic adaptation. Cholecystokinin (CCK) is well-known to be a potent trophic stimulus on the pancreas. On the other hand, the oral application of the synthetic trypsin inhibitor camostate results in an extensive release of endogenous CCK in rats, α-difluoromethylornithine (DFMO), an irreversible and specific inhibitor of ODC, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Camostate feeding (200 mg/kg b. wt. orally twice a day) resulted in a rapid elevation of ODC activity already after 2 hours, reaching a maximum after 6 hours (about 200fold above controls) followed by a significant increase in putrescine after 4 hours and sper-midine after 24 hours while spermine remained unchanged. The trophic parameters increased as expected in following timercourse: thymidine kinase (12 hours), DNA polymerase (12 hours), protein (24 hours), pancreatic weight (24 hours) and DNA (5 days). DFMO (2% in drinking water + 3×300 mg/kg b. wt. i. p. during daytime) was not able to prevent but significantly delayed and reduced the camostate-induced increase in ODC and polyamines as well as the trophic parameters. These data indicate an essential role for ODC and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation.

Keywords

Thymidine Kinase Ornithine Decarboxylase Polyamine Biosynthesis Intestinal Adaptation Pancreatic Enzyme Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    A. E. Pegg, and P. P. McCann, Polyamine metabolism and function, Am. J. Physiol. 243: C212 (1982).PubMedGoogle Scholar
  2. 2.
    C. W. Tabor, and H. Tabor, Polyamines, Aim. Rev. Biochem. 53: 749 (1984).CrossRefGoogle Scholar
  3. 3.
    A. Raina, and I. Jänne, Physiology of the natural polyamines putrescine, spermidine and spermine, Medical Biology 53: 121 (1975).PubMedGoogle Scholar
  4. 4.
    G. Luk, and S. Baylin, Polyamines and intestinal growth — increased polyamine biosynthesis after jejunectomy, Am. J. Physiol. 245: G656 (1983).PubMedGoogle Scholar
  5. 5.
    M. Hosomi, F. Lirussi, N. H. Stace, S. Vaja, G. M. Murphy, and R. H. Dowling, Mucosal polyamine profile in normal and adapting (hypo and hyperplastic) intestine: effects of DFMO treatment, Gut 28, s. 1: 103 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    G. Luk, L. Marton, and S. Baylin, Ornithine decarboxylase is important in intestinal mucosal maturation and recovery from injury in rats, Science 210: 195 (1980).CrossRefGoogle Scholar
  7. 7.
    P. Yang, S. B. Baylin, and G. D. Luk, Polyamines and intestinal growth: absolute requirement for ODC activity in adaptation during lactation, Am. J. Physiol. 247: G553 (1984).PubMedGoogle Scholar
  8. 8.
    R. H. Dowling, M. Hosomi, N. H. Stace, F. Lirussi, B. Miazza, H. Levan, and G. M. Murphy, Hormones and polyamines in intestinal and pancreatic adaptation, Scand. J. Gastroenterol. 20, suppl. 112: 84 (1985).CrossRefGoogle Scholar
  9. 9.
    G. D. Luk, and P. Yang, Polyamines in intestinal and pancreatic adaptation, Gut 28, suppl. 1: 95 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Haarstad, A. Winnberg, and H. Petersen, Effects of a cholecystokinin-like peptide on DNA and polyamine synthesis in the rat pancreas, Scand. J. Gastroenterol. 20: 530 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    J. Morisset, and O. Benrezzak, Polyamines and pancreatic growth induced by caerulein, Life Sci. 35: 2471 (1984).PubMedCrossRefGoogle Scholar
  12. 12.
    Chr. Löser, U. R. Fölsch, D. Mustroph, P. Cantor, U. Wunderlich, and W. Creutzfeldt, Pancreatic polyamine concentrations and cholecystokinin plasma levels in rats after feeding raw or heat-inactivated soybean flour, Pancreas 3: 285 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    U. R. Fölsch, K. Winckler, and K. G. Wormsley, Influence of repeated administration of cholecystokinin and secretin on the pancreas of the rat, Scand. J. Gastroenterol. 13: 663 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    B. Göke, H. Printz, I. Koop, U. Rausch, G. Richter, R. Arnold, and G. Adler, Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate), Pancreas 1: 509 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Otsuki, A. Ohki, Y. Okabayashi, I. Suehiro, and S. Baba, Effect of synthetic protease inhibitor camostate on pancreatic exocrine function in rats, Pancreas 2: 164 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    D. S. Louie, D. May, P. Miller, and C. Owyang, Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats, Am. J. Physiol. 250: G252 (1986).PubMedGoogle Scholar
  17. 17.
    U. R. Fölsch, P. Cantor, H. M. Wilms, A. Schafmayer, H. D. Becker, and W. Creutzfeldt, Role of cholecystokinin in the negative feedback control of pancreatic enzyme secretion in conscious rats, Gastroenterology 92: 449 (1987).PubMedGoogle Scholar
  18. 18.
    J. R. Wisner, R. E. McLaughlin, K. A. Rick, S. Ozawa, and I. G. Renner, Effects of L-364, 718 a new cholecystokinin receptor antagonist, on camostate-induced growth of the rat pancreas, Gastroeaterol. 94: 109 (1988).Google Scholar
  19. 19.
    Chr. Löser, U. Wunderlich, and U. R. Fölsch, Reversed-phase liquid chromatographic separation and simultaneous fluorimetric detection of polyamines and their monoacetyl derivatives in human and animal urine, serum and tissue samples — An improved, rapid and sensitive method for routine application, J. Chromatogr, in press (1988).Google Scholar
  20. 20.
    M. M. Bradford, A rapTd and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem. 72: 248 (1976).PubMedCrossRefGoogle Scholar
  21. 21.
    C. Labarca, and K. Paigen, A simple, rapid, and sensitive DNA assay procedure, Anal. Biochem. 102: 344 (1980).PubMedCrossRefGoogle Scholar
  22. 22.
    U. R. Fölsch, Regulation of pancreatic growth, Clin. Gastroenterol. 13: 679 (1984).PubMedGoogle Scholar
  23. 23.
    J. C. Romijn, C. F. Verkoelen, and T. A. W. Splinter, Problems of pharmacokinetic studies on alpha-difluoromethylornithine in mice, Cancer Chemother. Pharmacol. 19: 30 (1987).PubMedCrossRefGoogle Scholar
  24. 24.
    H. Pösö, and A. E. Pegg, Effect of α-difluoromethylornithine on polyamine and DNA synthesis in regenerating rat liver. Reversal of inhibition of DNA synthesis by putrescine, Biochim. Biophys. Acta 696: 179 (1982).PubMedGoogle Scholar
  25. 25.
    G. D. Luk, Essential role of polyamine metabolism in hepatic regeneration. Inhibition of DNA and protein synthesis and tissue regeneration by difluoromethylornithine in the rat, Gastroenterology 90: 1261 (1986).PubMedGoogle Scholar
  26. 26.
    O. Benrezzak, and J. Morisset, Effects of α-difluoromethylornithine on pancreatic growth induced by caerulein, Regul. Pept. 9: 143 (1984).PubMedCrossRefGoogle Scholar
  27. 27.
    J. Morisset, and O. Benrezzak, Reversal of α-difluoromethylornithine inhibition of caerulein-induced pancreatic growth by putrescine, Regul. Pept. 11: 201 (1985).PubMedCrossRefGoogle Scholar
  28. 28.
    J. Morisset, and G. Grondin, Implication of ornithine decarboxylase and polyamines in pancreatic growth of neonatal rats, Pancreas 2: 303 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Christian Löser
    • 1
  • Ulrike Cleffmann
    • 1
  • Frauke Alves
    • 1
  • Ulrich R. Fölsch
    • 1
  • Werner Creutzfeldt
    • 1
  1. 1.Div. of Gastroenterology and Endocrinology, Dept. of MedicineGeorg-August-UniversityGöttingenGermany

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