Inhibition of human colonic (Na++K+)-ATPase by arachidonic and linoleic acid |
| |
Authors: | Hubert Allgayer Lindsay Brown Wolfgang Kruis Erland Erdmann Gustav Paumgartner |
| |
Institution: | (1) Department of Internal Medicine I, Klinikum Großhadern, University of Munich, Marchioninistraße 15, D-8000 München 70, Germany;(2) Department of Internal Medicine II, Klinikum Großhadern, University of Munich, Marchioninistraße 15, D-8000 München 70, Germany |
| |
Abstract: | Summary 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 (K
D
1.9±0.2×10–9 mol/l) with a maximal binding capacity of 7.5±0.8×1014 binding sites/g protein. Both arachidonic and linoleic acid inhibited (Na++K+)-ATPase activity (IC50 arachidonic acid: 7.5×10–5 mol/l, linoleic acid: 6.5×10–5 mol/l) and Mg2+-ATPase activity (IC50 arachidonic acid: 9×10–5 mol/l, linoleic acid: 4×10–5 mol/l). Arachidonic acid inhibited 3H-ouabain binding, (IC50 3.2×10–5 mol/l). The following antiinflammatory compounds, at concentrations up to 1×10–3 mol/l, did not influence ATPase activity directly nor reverse the arachidonic acid-induced inhibition: indomethacin (cyclooxygenase inhibitor), nordihydroguaretic 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.Supported by DFG (Er65/4-4) |
| |
Keywords: | Colonic (Na++K+)-ATPase 3H-ouabain binding Inhibition arachidonic linoleic acid Sulphasalazine metabolites |
本文献已被 SpringerLink 等数据库收录! |
|