Agents and Actions

, Volume 5, Issue 5, pp 431–439 | Cite as

Diamine oxydase in rabbit small intestine: Separation from a soluble monoamine oxidase, properties and pathophysiological significance in intestinal ischemia

  • Jürgen Kusche
  • Hans Richter
  • Johanna Schmidt
  • Rudolf Hesterberg
  • Anne Friedrich
  • Wilfried Lorenz
Histamine and Kinins


From all mammals investigated so far only in rabbits diamine oxidase could not be detected in any tissue except the gut. Thus this species was chosen for studying the physiological and pathophysiological function of this enzyme in the gastrointestinal tract.

By gel filtration on Sephadex G 50 and G 200 the enzyme was purified 100-fold, separated from a soluble monoamine oxidase, and the properties of the two enzymes were determined. Diamine oxidase from rabbit small intestine deaminated putrescine (K m =1.3×10−4M, pH-optimum 6.4–6.9) and histamine (K m =8×10−5M, pH-optimum 7.5), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. Soluble monoamine oxidase from rabbit small intestine catabolized serotonin (K m =1.8×10−4M, pH-optimum 8.8), but not putrescine and histamine, and was inhibited by pargyline, but not by aminoguanidine.

Based on its properties in vitro intestinal diamine oxidase could inactivate the vasoactive biogenic amine histamine in vivo. To confirm this hypothesis, in rabbits the small intestine was damaged severely by inducing total intestinal ischemia, which occurs as mesenteric infarction also in human subjects and is accompanied by histamine release. Treatment with aminoguanidine and ischemia killed the animals 3-times faster than ischemia alone, which supported our hypothesis on a protective role of intestinal diamine oxidase against histamine.


Ischemia Serotonin Histamine Diamine Putrescine 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    C.H. Best,The Disappearance of Histamine from Autolysing Lung Tissue, J. Physiol.67, 256 (1929).Google Scholar
  2. [2]
    A.E. Zeller,Über den enzymatischen Abbau von Histamin und Diaminen, Helv. Chim. Acta21, 880 (1938).CrossRefGoogle Scholar
  3. [3]
    R. Kapeller-Adler,Purification and Identification of Hog-Kidney Histaminase, Biochim. Biophys. Acta67, 542 (1963).CrossRefGoogle Scholar
  4. [4]
    B. Mondovi, G. Rotilio, A. Finazzi andA. Scioscia-Santoro,Purification of Pig-Kidney Diamine Oxidase and its Identity with Histaminase, Biochem. J.91, 408 (1964).PubMedGoogle Scholar
  5. [5]
    F. Paolucci, L. Cronenberger, R. Plan andH. Pacheo,Purification et propriétés de la diamine: oxygène oxydoreductase du placenta humain, Biochemie53, 735 (1971).Google Scholar
  6. [6]
    W. Lorenz, J. Kusche andE. Werle,Über eine neue Methode zur Bestimmung der Diaminoxidase-Aktivität, Hoppe-Seylers Z. Physiol. Chem.348, 561 (1967).PubMedGoogle Scholar
  7. [7]
    W. Lorenz, J. Kusche, H. Hahn andE. Werle,Determination of the Activity of Diamine Oxidases, Urease and Histidine Ammonia Lyase by Enzymatic Assay of Ammonia, Z. analyt. Chem.243, 259 (1968).CrossRefGoogle Scholar
  8. [8]
    J. Kusche, H. Richter, R. Hesterberg, J. Schmidt andW. Lorenz,Comparison of the 14 C-Putrescine Assay with the NADH Test for the Determination of Diamine Oxidase: Description of a Standard Procedure with a High Precision and an Improved Accuracy, Agents and Actions3, 148 (1973).PubMedGoogle Scholar
  9. [9]
    D.H. Russell,The Roles of the Polyamines, Putrescine, Spermidine, and Spermine in Normal and Malignant Tissues, Life Sci.13, 1635 (1973).CrossRefPubMedGoogle Scholar
  10. [10]
    B. Hacker,Polyamines in Normal and Neoplastic Growth (Ed. D.H. Russel; Raven Press, New York 1973), p. 55.Google Scholar
  11. [11]
    J. Jännä andA. Raina,Stimulation of Spermidine Synthesis in the Regenerating Rat Liver: Relation to Increased Ornithine Decarboxylase Activity, Acta chem. scand.22, 1349 (1968).PubMedGoogle Scholar
  12. [12]
    R.G. Ham,Putrescine and Related Amines as Growth Factors for a Mammalian Cell Line, Biochem. Biophys. Res. Comm.14, 34 (1964).CrossRefPubMedGoogle Scholar
  13. [13]
    E. Werle andE. v. Pechmann,Über die Diaminoxydase der Pflanzen und ihre adaptive Bildung durch Bakterien, Justus Liebigs Ann. Chem.562, 44 (1949).Google Scholar
  14. [14]
    E. Werle, I. Trautschold andD. Aures,Reinigung und Charakterisierung der Diamin-Oxidase aus Erbsen, Hoppe-Seylers Z. Physiol. Chem.326, 200 (1961).PubMedGoogle Scholar
  15. [15]
    R. Kameswaran, J. N. Pennefather andG. B. West,Histamine and Rat Pregnancy, Proc. J. Physiol.162, 50 (1962).Google Scholar
  16. [16]
    A. L. Southren, Y. Kobayashi, W. Jung andA. B. Weingold,Metabolism of 14 C-Histamine Injected into the Fetal and Maternal Circulations of the Perfused Human Placenta in vitro, J. Clin. Endocrin. Metabol.28, 1724 (1968).Google Scholar
  17. [17]
    D.N. Danforth andF. Gorham,Placental Histaminase, Am. J. Physiol.119, 294 (1937).Google Scholar
  18. [18]
    R. Kapeller-Adler,Recent Attempts at the Purification and Identification of Human Placental ‘Histaminase’, Clin. Chim. Acta11, 191 (1965).CrossRefPubMedGoogle Scholar
  19. [19]
    J. Marcou, E. Athanasiu-Vergu, D. Chiriceanu, G. Cosma, N. Gingold andC.C. Parhon,Sur le rôle physiologique de l'histamine, Presse méd.46, 371 (1938).Google Scholar
  20. [20]
    A. Ahlmark,Studies on the Histaminolytic Power of Plasma with Special Reference to Pregnancy, Acta Physiol. scand.9, 1 (1944).Google Scholar
  21. [21]
    R. Kapeller-Adler,Investigations on the Activity of the Histaminase in Normal and Toxaemic Pregnancy, Biochem. J.38, 270 (1944).Google Scholar
  22. [22]
    J. Kusche, U. v. Trotha, G. Mühlberger andW. Lorenz,The Clinical-Chemical Application of the NADH Test for the Determination of Diamine Oxidase Activity in Human Pregnancy, Agents and Actions4, 188 (1974).PubMedGoogle Scholar
  23. [23]
    A. L. Southern, Y. Kobayashi, N.C. Carmody andA.B. Weingold,Serial Measurements of Plasma Diamine Oxidase during Normal Human Pregnancy by an Improved Method, 95, 615 (1966).Google Scholar
  24. [24]
    W. G. Bardsley, C. M. Hill andR. W. Lobley,A Reinvestigation of the Substrate Specificity of Pig Kidney Diamine Oxidase, Biochem. J.117, 169 (1970).PubMedGoogle Scholar
  25. [25]
    W. Schmutzler, H. Giertz, F. Hahn, G. Seseke andW. Bernauer,The Influence of Aminoguanidine and Heparine on Shock in Guinea-Pigs, Int. Arch. Allergy28, 48 (1965).Google Scholar
  26. [26]
    E. Werle andV. Schirren,Einfluss von Diaminoxidasegaben auf den anaphylaktischen Schock des Meerschweinchens, Z. ges. exp. Med.138, 522 (1965).PubMedGoogle Scholar
  27. [27]
    K.S. Kim, B. Backus, M. Harris andP. Rourke,Distribution of Diamine Oxidase and Imidazole-N-Methyltransferase along the Gastrointestinal Tract, Comp. Biochem. Physiol.31, 137 (1969).CrossRefPubMedGoogle Scholar
  28. [28]
    F. Buffoni,Histaminase and Related Amine Oxidases, Pharmac. Rev.18, 1163 (1966).Google Scholar
  29. [29]
    W. Lorenz, E. Matejka, A. Schmal, W. Seidel, H.-J. Reimann, R. Uhlig andG. Mann,A Phylogenetic Study on the Occurrence and Distribution of Histamine in the Gastrointestinal Tract and other Tissues of Man and Various Animals, Comp. Gen. Pharmac.4, 229 (1973).CrossRefGoogle Scholar
  30. [30]
    R.W. Fuller,Selective Inhibition of Monoamine Oxidase, Adv. Biochem. Psychopharmac.5, 339 (1972).Google Scholar
  31. [31]
    W. Schuler,Zur Hemmung der Diaminoxydase, Experientia8, 230 (1952).PubMedGoogle Scholar
  32. [32]
    T. Okuyama andY. Kobayashi,Determination of Diamine Oxidase Activity by Liquid Scintillation Counting, Arch. Biochem. Biophys.95, 242 (1961).CrossRefPubMedGoogle Scholar
  33. [33]
    T.E. Weichselbaum,Protein Determination by the Biuret Method, Am. J. Clin. Path.10, 40 (1946).Google Scholar
  34. [34]
    O.H. Lowry, N.J. Rosenbrough, A.L. Farr andR.J. Randall,Protein Measurement with the Folin Phenol Reagent, J. Biol. Chem.193, 265 (1951).PubMedGoogle Scholar
  35. [35]
    G.W. Snedecor andW.G. Cochran Statistical Methods (The Iowa State University Press, Ames, Iowa 1967).Google Scholar
  36. [36]
    H. Lineweaver andD. Burk,The Determination of Enzyme Dissoziation Constants, J. Am. Chem.56, 658 (1934).CrossRefGoogle Scholar
  37. [37]
    H. Richter, J. Kusche, K.-Th. Schumann, J. Schmidt andW. Lorenz,Diamine Oxidase and Histamine in the Small Intestine after Experimental Ischemia, Br. J. Surg.59, 912 (1972).Google Scholar
  38. [38]
    J. Kusche, H. Richter, R. Hesterberg andW. Lorenz,The Role of Humoral Factors and Diamine Oxidase Activity in Shock after Intestinal Ischaemia in Rabbits, Br. J. Surg.60, 904 (1973).Google Scholar
  39. [39]
    W. Schmutzler, K.D. Rämsch, W. Dingler, R. Lueb andA. Vaehsen,Complex Formation of Guinea-Pig Liver Diamine Oxidase (Histaminase) with Heparinoids, Agents and Actions4, 189 (1974).PubMedGoogle Scholar
  40. [40]
    J. Kusche, H. Richter, A. Friedrich, J. Schmidt, R. Hesterberg andW. Lorenz,Diamine Oxidase in the Small Intestine of Rabbits: Separation from a Soluble Monoaminoxidase and Alteration of the Activity by Intestinal Ischemia, Naunyn Schmiedebergs Arch. Pharmak. Suppl. to282, R53 (1974).Google Scholar
  41. [41]
    R. Kapeller-Adler,Amine Oxidases and Methods for their Study (Wiley-Interscience 1970), p. 32.Google Scholar
  42. [42]
    H.L. Luschinsky andH.O. Singer,Identification and Assay of Monoamine Oxidase in the Human Placenta, Arch. Biochem.19, 95 (1948).Google Scholar
  43. [43]
    W.G. Bardsley, M. James, C. Crabbe andJ. v. Scott,The Amine Oxidases of Human Placenta and Pregnancy Plasma, Biochem. J.139, 169 (1974).PubMedGoogle Scholar
  44. [44]
    F. Hahn, R. Kretschmar, H.J. Teschendorf andR. Mitze,Role of Histaminase (DAO) in Disappearance of Plasma Histamine in Anaphylaxis and after Histamine Injection, Int. Arch. Allergy39, 449 (1970).PubMedGoogle Scholar
  45. [45]
    J.L. Mongar andH.O. Schild,Potentiation of the Action of Histamine by Semicarbazide, Nature, Lond.167, 232 (1951).Google Scholar
  46. [46]
    O. Arunslakshana, J.L. Morgan andH.O. Schild,Potentiation of Pharmacological Effects of Histamine by Histaminase Inhibitors, J. Physiol.123, 32 (1954).PubMedGoogle Scholar
  47. [47]
    U.F. Gruber,Intestinale Faktoren im Schock: Darmtoxine, Langenb. Arch. klin. Chir.319, 909 (1967).Google Scholar
  48. [48]
    K. Messmer,Intestinale Faktoren im Schock: Intestinaler Kreislauf Langenb. Arch. klin. Chir.319, 890 (1967).Google Scholar
  49. [49]
    E.E. Kobold andA.P. Thal,Quantitation and Identification of Vasoactive Substances Liberated during Various Types of Experimental and Clinical Intestinal Ischemia, Surg. Gynecol. Obstet.117, 315 (1963).PubMedGoogle Scholar
  50. [50]
    W. Lorenz andG. Feifel,Neue Gesichtspunkte zur Pathogenese des Stress- und Steroidulkus, Dt. Med. Wschr.95, 1848 (1970).Google Scholar
  51. [51]
    G. Feifel, W. Lorenz, A. Hund andB. Zboralski,Die Bedeutung von Histamin bei der Pathogenese akuter Erosionen im Rattenmagen, Res. exp. Med.157, 206 (1972).CrossRefGoogle Scholar
  52. [52]
    O. Sjaastad,Histamine Formation and Catabolism in the Faeces with Special Reference to Dystrophia Myotonica, Scand. J. Gastroenterol.1, 173 (1966).PubMedGoogle Scholar
  53. [53]
    E. Werle andA. Raub,Über Vorkommen, Bildung und Abbau biogener Amine bei Pflanzen unter besonderer Berücksichtigung des Histamins, Biochem. Z.318, 538 (1948).Google Scholar

Copyright information

© Birkhäuser Verlag 1975

Authors and Affiliations

  • Jürgen Kusche
    • 1
  • Hans Richter
    • 1
  • Johanna Schmidt
    • 1
  • Rudolf Hesterberg
    • 1
  • Anne Friedrich
    • 1
  • Wilfried Lorenz
    • 1
  1. 1.Abteilung für Experimentelle Chirurgie und Pathologische Biochemie an der Chirurgischen Klinik der UniversitätMarburg a.d. LahnFederal Republic of Germany

Personalised recommendations