EFFECT OF INDOMETHACIN ON H+ TRANSPORTATION OF PIG GASTRIC H+/K+-ATPase
Du Jian Lin Zhi-huan Li Sheng-guang (Division of Biomembrane, Institute of Biophysics, Chinese Academy of Science, Beijing 100101)
As a noncompetitive inhibitor of pig gastric H+/K+-ATPase, indomethacin inhibited the H+ transportation function of the enzyme, leading to not only the obvious dissipation of H+/K+-ATPase-gene-rated H+ gradients, but also the deceasing of the H+ gradient formation ability of the enzyme. 4% of indomethacin was able to penetrate into the lipid bilayer of H+/ K+-ATPase vesicles at 0.15mg/ml protein concentration, which showed an influence of indomethacin to the membrane. Indome- thacin reduced the membrane fluidity of H+/K+-ATPase vesicles significantly. It also damaged the conformation of membrane protein extraordinarily, which was evidenced by decreasing the intrinsic fluorescence of H+/K+-ATPase. From the results, we suggest that the effect of indomethacin on H+/K+-ATPase is taken place by its inhibition on H+/K+-ATPase protein, as well as by its influence on the membrane lipid bilayer of H+/K+-ATPase vesicles.