Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase. A possible diarrhogenic factor?
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 4.0 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 capacity of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.
Allgemeine Innere Medizinische Klinik (Schwerpunkt Gastroenterologie-Hepatologie), Rheinische Friedrich-Wilhelms-Universität Bonn.
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C
Scheurlen
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Allgayer
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W
Kruis
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Erdmann
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Sauerbruch
D000636:Aminosalicylic Acids / Q000009:adverse effects*; D001667:Binding, Competitive; D012809:Colon, Sigmoid / Q000201:enzymology; D003967:Diarrhea / Q000139:chemically induced*; D006801:Humans; D007082:Ileum / Q000201:enzymology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology*; D019804:Mesalamine; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000187:drug effects
D000636:Aminosalicylic Acids; D019804:Mesalamine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; C032587:olsalazine