Inhibition of human colonic (Na+ + K+)-ATPase by arachidonic and linoleic acid.

The sodium pump, (Na+ + K+)-ATPase, which is involved in the transport of cations and water movement by the colonic mucosa, may be decreased in various diarrhoeal states. In this study, we have measured 3H-ouabain binding and (Na+ + K+)-ATPase activity in human colonic biopsy homogenates and the influence of various inflammatory and antiinflammatory compounds on these parameters. 3H-ouabain binds to one site of high affinity (KD 1.9 +/- 0.2 X 10(-9) mol/l) with a maximal binding capacity of 7.5 +/- 0.8 X 10(14) binding sites/g protein. Both arachidonic and linoleic acid inhibited (Na+ + K+)-ATPase activity (IC50 arachidonic acid: 7.5 X 10(-5) mol/l, linoleic acid: 6.5 X 10(-5) mol/l) and Mg2+-ATPase activity (IC50 arachidonic acid: 9 X 10(-5) mol/l, linoleic acid: 4 X 10(-5) mol/l). Arachidonic acid inhibited 3H-ouabain binding, (IC50 3.2 X 10(-5) mol/l). The following antiinflammatory compounds, at concentrations up to 1 X 10(-3) mol/l, did not influence ATPase activity directly nor reverse the arachidonic acid-induced inhibition: indomethacin (cyclooxygenase inhibitor), nordihydroguaiaretic acid (lipoxygenase inhibitor), sulphasalazine and its metabolites: 5-aminosalicylic acid, N-acetylaminosalicylic acid and sulphapyridine. These results indicate that human colonic (Na+ + K+)-ATPase is inhibited by the prostanoid precursors, arachidonic and linoleic acid. From a therapeutic point of view (effect on colonic (Na+ + K+)-ATPase and perhaps diarrhoea), the suppression of the production of these prostanoid precursors by drugs may, therefore, be beneficial in the treatment of inflammatory bowel disease.