The clinical investigator

, Volume 71, Issue 4, pp 286–289 | Cite as

Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase

A possible diarrhogenic factor?
  • C. Scheurlen
  • H. Allgayer
  • W. Kruis
  • E. Erdmann
  • T. Sauerbruch
Original Article


Olsalazine (azodisalicylate) and mesalazine (5-aminosalicylic acid) have recently been developed as new treatment modalities for inflammatory bowel disease to avoid sulfasalazine-related side effects. However, there are reports regarding new and hitherto unexpected side effects in some patients receiving olsalazine or mesalazine, such as watery diarrhea. Since sodium pump activities play an important role in the pathogenesis of water and electrolyte disturbances, we investigated the influence of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase and its specific [3H]-ouabain binding. We found a concentration-dependent inhibition of ileal and colonic (Na+ + K+)-ATPase by olsalazine with an IC50 of 4.1 mM and 4.8 mM, respectively. Mesalazine inhibited this enzyme in the ileum with an IC50 of 4.5 mM and in the sigmoid colon with an IC50 3.5 mM. In addition, [3H]-ouabain binding was inhibited by mesalazine with an IC50 of 3.6 mM. The maximal inhibition, however, did not exceed 80% under any conditions (up to 10 mM drug concentration). Olsalazine and mesalazine induce inhibition of the ileal and colonic sodium pump activities that may (in addition to other possible mechanisms) mediate impaired water and electrolyte absorption. This is possibly of clinical relevance in patients with severely damaged mucosa. In patients with milder forms of mucosal inflammation, this inhibition most likely is of minor importance because of the great capacitiy of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.

Key words

(Na+ + K+)-ATPase Inflammatory bowel disease Diarrhea 5-Aminosalicyclic acid Olsalazine Mesalazine 



5-aminosalicylic acid


ethylenediaminetetracetic acid


inflammatory bowel disease


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    1.Allgayer H (1992) Sulfasalazine and 5-ASA compounds. Gastroenterol Clin North Am 21:643–658Google Scholar
  2. 2.
    Allgayer H, Brown L, Kruis W, Erdmann E, Paumgartner G (1986) Inhibition of human colonic (Na+ + K+)-ATPase by arachidonic and linoleic acid. Naunyn Schmiedebergs Arch Pharmacol 332:398–402Google Scholar
  3. 3.
    Allgayer H, Brown L, Kruis W, Paumgartner G, Erdmann E, Wiebecke B (1988) Inverse relationship between colonic (Na+ + K+)-ATPase activity and the degree of mucosal inflammation in inflammatory bowel disease. Dig Dis Sci 33:417–422Google Scholar
  4. 4.
    Austin CA, Cann PA, Jones TH, Holdsworth CD (1984) Exacerbation of diarrhea and pain in patients treated with 5-amino salicyclic acid for ulcerative colitis. Lancet I:917–918Google Scholar
  5. 5.
    Chakraborthy TK, Bhatia D, Heading RC, Ford MJ (1987) Salicylate induced exacerbation of ulcerative colitis. Gut 28:613–615Google Scholar
  6. 6.
    Eiderhamin J, Finkel Y, Starndvik B (1989) Na,K-ATPase activity in rectal mucosa of children with ulcerative colitis and Crohn's disease. Scand J Gastroenterol 24:1121–1125Google Scholar
  7. 7.
    Evans DF, Pye G, Bramley T, Clark AG, Dyson TJ, Hardcastle JD (1988) Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 29:1035–1041Google Scholar
  8. 8.
    Goerg KJ, Wanitschke K, Gabbert H, Breiling J, Frank M, Meyer zum Büschenfelde KH (1987) Azodisalicylate (azodisal sodium) causes intestinal secretion. Digestion 37:79–87Google Scholar
  9. 9.
    Jarnerot G (1989) Newer 5-aminosalicylic acid based drugs in chronic inflammatory bowel disease. Drugs 37:73–86Google Scholar
  10. 10.
    Lauritsen K, Laursen LS, Burkhave K, Rask-Madsen J (1988) Colonic prostaglandin E2 levels and olsalazine metabolism in relapsing ulcerative colitis: implications for controlled trials in the long term. Scand J Gastroenterol 23 [Suppl 148]:76–80Google Scholar
  11. 11.
    Lauritsen K, Laursen LS, Rask-Madsen J (1990) Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal disease. II. Clin Pharmacokinet 19:94–125Google Scholar
  12. 12.
    Laursen LS, Stokholm M, Burkhave K, Rask-Madsen J, Lauritsen K (1990) Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. Gut 31:1271–1276Google Scholar
  13. 13.
    Lowry OH, Rosebrough NJ, Farr AC, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 93:265–275Google Scholar
  14. 14.
    Mohsen AQM, Mulvey D, Priddle JD, Parsons DS, Jewell DP (1987) Effects of olsalazine in the jejunum of the rat. Gut 28:346–352Google Scholar
  15. 15.
    Mulder CL, Tytgat GN, Weterman IT, Dekker W, Blok P, Schrijver M, van der Heide H (1988) Double-blind comparison of slow-release 5-ASA and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology 95:1449–1453Google Scholar
  16. 16.
    Rachmilewitz D, Treves AJ, Ligumski M, Sharon P, Zifroni H, Karmeli F (1982) Possible role of prostanoids as mediators in the pathogenesis of inflammatory bowel disease. In: Rachmilewitz D, Pena A (eds) Inflammatory bowel diseases. Nijhoff, Hague, pp 161–173Google Scholar
  17. 17.
    Riley SA, Turnberg LA (1990) Sulphasalazine and the aminosalicylates in the treatment of inflammatory bowel disease. Q J Med 75:551–562Google Scholar
  18. 18.
    Robinson MG (1989) New oral salicylates in the therapy of chronic inflammatory bowel disease. Gastroenterol Clin North Am 18:43–50Google Scholar
  19. 19.
    Sandberg-Gertzen H, Jarnerot G, Kraaz W (1986) Azodisal sodium in the treatment of ulcerative colitis. A study of tolerance and relapse prevention properties. Gastroenterology 90:1024–1030Google Scholar
  20. 20.
    Scheurlen C, Wedel S, Zwiebel FM, Kruis W, Allgayer H, Scholz R (1992) Olsalazine related diarrhoea: does rat intestine adapt in vivo? Scand J Gastroenterol 27:311–316Google Scholar
  21. 21.
    Schoner W, von Ilberg C, Kramer R, Seubert W (1967) On the mechanism of Na+- and K+-stimulated hydrolysis of adenosine triphosphate. I. Purification and properties of a Na+- and K+-activated ATPase from ox brain. Eur J Biochem 1:334–343Google Scholar
  22. 22.
    Tripp JM, Müller DDR, Harris D Jr (1980) Mucosal (Na+ + K+)-ATPase and adenylate cyclase activities in children with toddler diarrhea and the postenteritis syndrome. Pediatr Res 14:1382–1386Google Scholar
  23. 23.
    Wadworth AN, Fitton A (1991) Olsalazine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease. Drugs 41:647–664Google Scholar
  24. 24.
    Wanitschke R, Goerg KJ, Jeschek B, Krok S (1987) The effect of azodisalicylate on net electrolyte and water transfer in the intact healthy human colon. Abstract. Gastroenterology 92:1685Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • C. Scheurlen
    • 1
    • 5
  • H. Allgayer
    • 2
  • W. Kruis
    • 3
  • E. Erdmann
    • 4
  • T. Sauerbruch
    • 1
  1. 1.Allgemeine Innere Medizinische Klinik (Schwerpunkt Gastroenterologie-Hepatologie)Rheinische Friedrich-Wilhelms-UniversitätBonn
  2. 2.Medizinische Klinik, Städtisches Krankenhaus KarlsruheGermany
  3. 3.Abteilung für Innere Medizin, Evangelisches Krankenhaus Köln-KalkGermany
  4. 4.Medizinische Klinik I, Klinikum Gro\hadernLudwig-Maximilians-Universität MünchenGermany
  5. 5.Allgemeine Innere Medizin der RheinFriedrich-Wilhelm-Universität BonnBonn - VenusbergGermany

Personalised recommendations